An Expert Report on the Radiopharmaceutical 18F-PSMA-1007

I. Introduction to 18F-PSMA-1007

A. Overview of 18F-PSMA-1007 as a PET Radiotracer

[18F-PSMA-1007 is a novel diagnostic radiopharmaceutical designed for Positron Emission Tomography (PET) imaging. It specifically targets the Prostate-Specific Membrane Antigen (PSMA), a protein that is notably overexpressed on the surface of prostate cancer cells.][1][ As a fluorine-18 (18F) labeled PSMA-targeting ligand, 18F-PSMA-1007 enables the visualization of PSMA-positive lesions through PET imaging, offering detailed information about the extent and location of the disease.][2]

[The development of PSMA-targeted PET tracers, including 18F-PSMA-1007, represents a significant advancement in the field of prostate cancer diagnostics.][2][ These agents aim to provide enhanced diagnostic accuracy compared to conventional imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI), thereby facilitating improved patient management strategies.][1][ 18F-PSMA-1007 is particularly recognized for its favorable imaging characteristics, which contribute to its growing clinical utility.][1][ The clinical value and novelty of 18F-PSMA-1007 are not solely derived from its ability to target PSMA, a characteristic shared by a class of similar agents. Its distinction lies significantly in the advantages conferred by the 18F radionuclide—such as a longer half-life enabling centralized production and potentially better image resolution than 68Ga-labeled agents—and its unique pharmacokinetic profile, most notably its predominant hepatobiliary excretion. This excretion pathway contrasts with the renal clearance of many other PSMA tracers, including 68Ga-PSMA-11 and some other 18F-labeled PSMA agents like 18F-DCFPyL, suggesting a specific developmental aim to optimize imaging in certain anatomical regions, particularly the pelvis where bladder activity from renally excreted tracers can be problematic.][4]

B. Significance in Prostate Cancer Imaging and Management

[Prostate cancer (PCa) ranks as one of the most frequently diagnosed malignancies among men worldwide and is characterized by a broad spectrum of clinical behaviors.][1][ Consequently, the accurate staging of the disease at initial diagnosis and the precise detection of recurrence are of paramount importance for guiding effective treatment decisions and improving oncological outcomes.][1][ 18F-PSMA-1007 PET/CT has emerged as an increasingly utilized imaging modality for these critical clinical scenarios, including the initial staging of patients with high-risk prostate cancer, the detection of sites of disease in patients experiencing biochemical recurrence (BCR), and informing the selection and planning of salvage therapies.][1]

[A significant challenge in prostate cancer management is the accurate localization of recurrent disease, particularly in patients with BCR who present with low or subtly rising prostate-specific antigen (PSA) levels, where conventional imaging techniques often yield negative or equivocal results.][2][ 18F-PSMA-1007 PET/CT aims to address this diagnostic gap. Clinical evidence suggests that the use of 18F-PSMA-1007 can lead to substantial changes in diagnostic interpretation and subsequently alter patient management plans.][10][ The clinical impact of 18F-PSMA-1007, therefore, extends beyond merely improving the sensitivity of lesion detection. It plays a crucial role in facilitating a more personalized and precise approach to prostate cancer care. By enabling earlier and more accurate characterization of the disease extent—such as upstaging at initial diagnosis or pinpointing the location of recurrence even at very low PSA levels—18F-PSMA-1007 PET/CT allows for the formulation of more tailored treatment strategies. This can lead to the selection of potentially curative-intent therapies in appropriately staged patients or help avoid futile local treatments when occult metastatic disease is identified, thereby optimizing therapeutic benefit and minimizing unnecessary morbidity.][1]

II. Chemical and Radiopharmaceutical Profile

A. Nomenclature (Synonyms, Developmental Codes)

[The radiopharmaceutical is most commonly identified as 18F-PSMA-1007 or [18F]PSMA-1007.][1][ Its Chemical Abstracts Service (CAS) Registry number is 2093321-19-6.][14][ A variety of synonyms are used in literature and databases, including Fluorine-18-PSMA-1007, PSMA-1007 F-18, F-18-PSMA-1007, FLUORINE(18F) PSMA-1007, and (18F)-PSMA-1007.][15][ In several European countries, the medicinal product containing [18F]PSMA-1007 as the active substance is marketed under the brand name Radelumin.][17] The consistent use of these identifiers is crucial for accurate scientific communication, regulatory affairs, and clinical practice. The availability of a branded product like Radelumin indicates its formal approval and commercial distribution in certain regions, signifying its established role in clinical diagnostics.

B. Chemical Structure and Molecular Formula

[The molecular formula of 18F-PSMA-1007 is C49​H55​FN8​O16​.][14][ Structurally, it is classified as a Glu-Ureido-type PSMA inhibitor.][16][ This structural motif, often referred to as a Glu-Urea-Glu (EuE) backbone, is a common pharmacophore in many high-affinity PSMA inhibitors. The fluorine-18 (18F) atom, the positron-emitting radionuclide, is covalently attached to the ligand structure, typically as part of a fluoronicotinic acid moiety.][26]

[The specific chemical design of PSMA-1007, which includes not only the PSMA-binding pharmacophore but also modifications such as the incorporation of additional hydrophilic groups alongside the 18F-fluoronicotinic acid, is a deliberate strategy.][26][ These structural features are engineered to achieve a balance between high-affinity PSMA binding and a desirable pharmacokinetic profile. Notably, these modifications contribute to its characteristic lipophilicity (logP = -1.6) and high plasma protein binding (98%) ][25], which in turn are key determinants of its predominantly hepatobiliary excretion pathway. This carefully engineered molecular structure distinguishes 18F-PSMA-1007 from other PSMA ligands that may possess different physicochemical properties leading to alternative clearance mechanisms, such as greater renal excretion.

C. Radioisotope: Fluorine-18 (18F) Properties

[Fluorine-18 (18F) is the positron-emitting radioisotope integral to 18F-PSMA-1007. It possesses a physical half-life of approximately 109.7 minutes (commonly rounded to 110 minutes).][5][ The maximum energy of the positrons emitted by 18F is 0.634 MeV (634 keV), which is notably lower than that of Gallium-68 (68Ga), another radionuclide used in PSMA PET imaging.][7]

[The selection of 18F as the labeling radionuclide for PSMA-1007 offers several distinct advantages that contribute to its clinical utility and logistical feasibility. The relatively long half-life of ~110 minutes allows for centralized cyclotron production of 18F, followed by radiolabeling, comprehensive quality control, and subsequent distribution to multiple PET imaging centers, including those that do not have on-site cyclotron facilities. This operational model is often referred to as the "satellite concept".][8][ Furthermore, the lower positron energy of 18F translates to a shorter travel distance of the emitted positrons within tissues before they undergo annihilation. This physical characteristic results in improved spatial resolution and potentially sharper images in PET scans compared to those obtained with 68Ga, which has a higher positron energy.][5][ Additionally, 18F production via cyclotron allows for larger batch sizes, which can be more cost-effective and meet the demands of a higher number of patient scans compared to generator-produced isotopes like 68Ga.][7] These combined properties underscore a strategic technological preference for 18F in the development of new PET radiopharmaceuticals, aiming to enhance image quality, improve accessibility, and optimize production logistics.

D. Formulation, Radiolabeling Procedures, and Quality Control Standards

[18F-PSMA-1007 is supplied as a sterile solution for intravenous injection.][19][ The active pharmaceutical ingredient (API) is [18F]F-PSMA-1007. For instance, Radelumin multidose vials contain a radioactive concentration that allows for activities typically ranging from 7000 to 18,200 MBq at the Activity Reference Time (ART), in a final volume of approximately 23 mL.][29][ The formulation includes several excipients to ensure stability, isotonicity, and physiological pH. These commonly include phosphate buffer saline (containing disodium phosphate, potassium dihydrogen phosphate, sodium chloride, and potassium chloride), ethanol (e.g., up to 8% w/v in Radelumin), sodium ascorbate (as a stabilizer), and water for injections.][20]

[The radiolabeling of PSMA-1007 with 18F is typically performed using automated synthesis modules, such as the AllInOne (TRASIS) or Synthera® systems.][28][ A key advancement in its production is the use of an optimized precursor molecule that allows for a one-step direct nucleophilic substitution reaction with [18F]fluoride, without the need for protecting groups.][28][ This simplifies the synthesis process and can improve yields and reduce synthesis time, reported to be around 40 minutes.][34][ Radiochemical yields are generally in the range of 40-52% (non-decay corrected).][30]

[Stringent quality control (QC) procedures are mandatory and must comply with pharmacopoeial standards, such as those outlined in the European Pharmacopoeia.][30] QC tests for the final product include:

• Appearance[: Clear, colorless or slightly yellow solution, free from visible particles.][20]
• pH[: Typically between 4.5 and 8.5.][20]
• Identity[: Confirmed by gamma spectrometry (detection of 511 keV and 1022 keV annihilation photons), half-life determination (105–115 min), and High-Performance Liquid Chromatography (HPLC) retention time compared to a reference standard.][29]
• Radiochemical Purity (RCP)[: Assessed by HPLC and Thin Layer Chromatography (TLC), with acceptance criteria typically ≥95% for [18F]PSMA-1007 and limits on free [18F]fluoride (e.g., ≤5%).][29]
• Chemical Purity[: Limits for the non-radioactive PSMA-1007 precursor and other potential chemical impurities, often assessed by HPLC.][29][ Residual solvents like ethanol and Dimethyl Sulfoxide (DMSO) are also quantified (e.g., by Gas Chromatography, GLC).][29]
• Radionuclidic Purity[: Verification that 18F is the primary radionuclide and that long-lived impurities are within acceptable limits, typically checked post-release by gamma spectrometry.][29]
• Sterility and Bacterial Endotoxins[: The product must be sterile and meet limits for bacterial endotoxins (e.g., ≤175 EU/V or ≤20 EU/V depending on the source).][29][ Filter integrity tests (Bubble Point Test) are performed pre-release.][29]

[The successful production of [18F]PSMA-1007 using [18F]F- acquired from external suppliers (i.e., facilities without an on-site cyclotron) has been demonstrated, underscoring the importance of a robust quality assurance system to ensure final product consistency and safety regardless of the [18F]F- source.][30] This capability significantly broadens the potential clinical availability of 18F-PSMA-1007.

E. Storage, Stability, and Shelf-life of the Radiolabeled Product

[The radiolabeled product, [18F]PSMA-1007, in its final formulated solution for injection (e.g., Radelumin), typically possesses a shelf-life of 12 hours from the activity reference time (ART).][20] This extended shelf-life, relative to 68Ga-labeled radiopharmaceuticals, is a direct benefit of the ~110-minute physical half-life of the 18F radionuclide.

[Storage conditions generally specify maintaining the product at controlled room temperature, for example, not exceeding 30°C for Radelumin.][20][ It is crucial to protect the solution from light and moisture.][16] All storage and handling must comply with national regulations pertaining to radioactive materials.

[Studies have confirmed the stability of [18F]PSMA-1007, with no significant radiolysis (decomposition due to its own radiation) observed for up to 8 hours after the end of synthesis.][31][ For multi-dose vials, while chemical and physical stability is demonstrated for 12 hours from ART even after the first withdrawal, immediate use is generally recommended from a microbiological safety perspective unless the withdrawal is performed using validated aseptic techniques.][20][ If not used immediately, the in-use storage times and conditions become the responsibility of the user, but the product must be used before the expiration time.][20]

[In contrast, the non-radioactive PSMA-1007 precursor ligand, typically in powder form, requires different storage conditions for long-term stability, often at -20°C for months to years, or 0-4°C for short-term storage.][16]

[The practical implication of the 12-hour shelf-life and demonstrated stability of [18F]PSMA-1007 is substantial. It underpins the feasibility of the "satellite pharmacy" or centralized distribution model.][28][ A single radiopharmacy equipped with a cyclotron and automated synthesis modules can produce larger batches of [18F]PSMA-1007 and distribute ready-to-inject doses to multiple surrounding PET imaging centers that may not have their own production capabilities. This logistical advantage significantly enhances patient access to advanced PSMA PET imaging compared to tracers with very short half-lives that necessitate on-site production.][8]

Table 1: Key Radiopharmaceutical Properties of 18F-PSMA-1007

Property	Detail	Snippet Source(s)
Synonyms	F-18-PSMA-1007, Fluorine-18-PSMA-1007, (18F)-PSMA-1007, Radelumin (brand)	15
CAS Registry Number	2093321-19-6	14
Molecular Formula	C49​H55​FN8​O16​	14
Radioisotope	Fluorine-18 (18F)	2
Half-life of 18F	~109.7 minutes (approx. 110 minutes)	5
Positron Energy (Max)	0.634 MeV	7
Typical Injected Activity	3-4 MBq/kg; or 3.6-4.4 MBq/kg (Radelumin); max ~400-450 MBq	18
Shelf-life (Radiolabeled)	12 hours from ART (e.g., Radelumin)	20
Storage (Radiolabeled)	Below 30°C (Radelumin); protect from light and moisture	20

III. Mechanism of Action

A. Molecular Target: Prostate-Specific Membrane Antigen (PSMA)

[The primary molecular target of 18F-PSMA-1007 is the Prostate-Specific Membrane Antigen (PSMA).][2][ PSMA is a type II transmembrane glycoprotein that exhibits carboxypeptidase and folate hydrolase activity.][2][ It is also known by other names, including glutamate carboxypeptidase II (GCPII) in the context of neuronal glutamate synthesis, and folate hydrolase 1 (FOLH1), which refers to its encoding gene.][36][ The PSMA protein has a significant extracellular domain, which serves as the binding site for PSMA-targeted ligands like the one incorporated into 18F-PSMA-1007.][36]

[PSMA is highly overexpressed on the cell surface of prostate cancer cells, often by a factor of 100 to 1000 times more than in benign prostatic tissues or most other normal cells in the body.][2] This overexpression is observed in primary prostate cancer, as well as in metastatic lesions, including lymph node and bone metastases. Furthermore, PSMA expression levels tend to increase with tumor grade, pathological stage, androgen independence, and in metastatic or castration-resistant prostate cancer, making it a valuable biomarker for disease aggressiveness and progression. This pronounced and relatively selective overexpression in malignant prostatic tissue forms the basis for its utility as an excellent target for both diagnostic imaging with agents like 18F-PSMA-1007 and for PSMA-targeted radioligand therapies.

[It is crucial to recognize, however, that despite its name implying exclusivity to the prostate, PSMA expression is not entirely restricted to prostate tissue. Physiological (normal) expression of PSMA, albeit generally at lower levels than in prostate cancer, occurs in several other tissues. These include the salivary glands (particularly the parotid and submandibular glands), lacrimal glands, kidneys (proximal tubules), small intestine (duodenum and jejunum), liver, spleen, and sympathetic ganglia such as the coeliac and stellate ganglia.][4][ Additionally, PSMA expression has been identified in the neovasculature (newly formed blood vessels) of various non-prostatic malignant tumors, such as glioblastoma, renal cell carcinoma, hepatocellular carcinoma, and breast cancer, among others.][4][ This broader expression pattern means that PSMA-targeted PET imaging can show uptake in these normal sites and potentially in other cancers. Consequently, careful image interpretation, always in conjunction with anatomical imaging (CT or MRI) and the patient's clinical history, is essential to differentiate physiological uptake and non-prostatic tumor uptake from true prostate cancer lesions, thereby avoiding potential misdiagnosis.][19]

B. Binding Affinity and Specificity

[18F-PSMA-1007 is a Glu-Ureido-type PSMA inhibitor, a class of compounds known for their strong and selective interaction with the PSMA protein.][16][ It demonstrates high binding affinity for PSMA, which is a critical characteristic for an effective PET imaging agent. Quantitative measurements of this affinity, typically expressed as the half-maximal inhibitory concentration (IC50), indicate potent binding. For the non-radioactive F-PSMA-1007 ligand, an IC50 value of 4.2 ± 0.5 nM has been reported in competitive binding assays using LNCaP human prostate cancer cells, which naturally express PSMA.][25] This high affinity ensures that the radiotracer effectively binds to PSMA-expressing tumor cells even when present at low concentrations, contributing to sensitive lesion detection.

[The specificity of 18F-PSMA-1007 for PSMA is also high. This means it preferentially binds to PSMA over other cellular targets, minimizing non-specific background signal and enhancing the tumor-to-background contrast in PET images. In vitro studies have further revealed that [18F]PSMA-1007 undergoes significant internalization into PSMA-expressing cells after binding to the receptor on the cell surface.][4][ This internalization process, where the radiotracer-PSMA complex is drawn into the cell, can contribute to prolonged retention of radioactivity within the tumor cells.][3] This prolonged retention is advantageous for imaging, as it can lead to improved image quality and higher tumor-to-background ratios, especially at later imaging time points.

[The combination of high-affinity binding to the extracellular domain of PSMA, coupled with efficient internalization, is a defining feature of many successful PSMA-targeted radiopharmaceuticals, including 18F-PSMA-1007. These molecular interaction dynamics are fundamental not only for achieving sensitive diagnostic imaging but also form the basis for the development of theranostic PSMA agents, where a diagnostic ligand is paired with a therapeutic counterpart carrying a cytotoxic radionuclide. The structural similarities of 18F-PSMA-1007 to theranostic compounds like PSMA-617 ][4] suggest that the underlying mechanisms of binding and internalization are conserved and desirable for both diagnostic and therapeutic applications targeting PSMA.

C. Principle of PET Imaging with 18F-PSMA-1007

[The principle of PET imaging with 18F-PSMA-1007 relies on the selective accumulation of the radiotracer in tissues that express PSMA, followed by the detection of radiation emitted from the 18F radionuclide. After intravenous administration, 18F-PSMA-1007 circulates through the bloodstream and, due to the high affinity and specificity of its ligand component, binds to PSMA proteins present on the surface of cells, most notably prostate cancer cells.][2]

[The fluorine-18 (18F) atom within the 18F-PSMA-1007 molecule is unstable and undergoes radioactive decay by positron emission. A positron is an anti-electron (a particle with the same mass as an electron but with a positive charge). Once emitted, the positron travels a very short distance in the surrounding tissue (typically a few millimeters, depending on tissue density and the positron's initial energy) before it loses its kinetic energy and interacts with an electron. This interaction results in the annihilation of both the positron and the electron, converting their mass into energy in the form of two 511 keV gamma photons. These two gamma photons are emitted in almost exactly opposite directions (180° ± 0.25°).][2]

[A PET scanner is designed with a ring of detectors that can identify these pairs of coincident gamma photons. When two photons strike opposing detectors within a very short time window (a few nanoseconds), the scanner registers this as an annihilation event. By analyzing the lines of response from many such events, a computer algorithm can reconstruct a three-dimensional image that maps the distribution and concentration of the 18F radionuclide within the patient's body. Areas with higher concentrations of 18F-PSMA-1007, such as PSMA-expressing prostate cancer lesions, will appear as regions of increased signal intensity or "hot spots" on the PET image.][2][ This allows for the non-invasive, whole-body assessment of PSMA expression, facilitating the detection and localization of primary prostate tumors, regional lymph node involvement, and distant metastases in bone or soft tissues.][2] The co-registration of PET data with anatomical imaging from CT (in PET/CT) or MRI (in PET/MRI) provides precise anatomical localization of these PSMA-avid foci.

IV. Development and Regulatory Landscape

A. Development History: Key Milestones and Developers

[The development of 18F-PSMA-1007 can be traced back to 2016, originating from the German Cancer Research Centre (DKFZ) in Heidelberg, Germany. Key figures in its initial development include Cardinale et al. and Giesel et al..][12] Their work focused on creating a PSMA-targeting ligand that could be labeled with fluorine-18 and would exhibit favorable pharmacokinetic properties, particularly low urinary excretion, to improve pelvic imaging in prostate cancer.

[Following its initial development at DKFZ, ABX advanced biochemical compounds GmbH, a company specializing in radiochemicals and radiopharmaceuticals, licensed 18F-PSMA-1007 in 2016.][28][ ABX then took on the subsequent clinical development, conducting various clinical studies, including pivotal Phase III trials, to evaluate its safety and efficacy.][28] This progression from academic research to industry-led clinical development is a common pathway for bringing novel radiotracers into clinical practice.

[Further expanding its reach, the Centre for Probe Development and Commercialization (CPDC) in Canada also licensed [18F]PSMA-1007 from ABX. CPDC has been responsible for its development and clinical trial execution in Canada, including a Phase 3 trial aimed at securing regulatory approval from Health Canada.][43] These collaborations and licensing agreements are crucial for advancing the radiopharmaceutical through the rigorous stages of clinical testing and regulatory review across different global regions.

B. Licensing Agreements

The dissemination and broader clinical development of 18F-PSMA-1007 have been facilitated through a series of key licensing agreements:

1. German Cancer Research Centre (DKFZ) to ABX advanced biochemical compounds GmbH[: The foundational license was granted by DKFZ, the originating institution, to ABX in 2016. This agreement allowed ABX to undertake further development, manufacturing, and commercialization efforts.][28]
2. ABX advanced biochemical compounds GmbH to Centre for Probe Development and Commercialization (CPDC)[: CPDC obtained an exclusive license from ABX to develop, manufacture, and distribute [18F]PSMA-1007 in Canada.][43] This partnership is pivotal for making the agent available to Canadian patients, pending regulatory approval.
3. CPDC to Lawson Health Research Institute[: As part of its strategy to expand access within Canada, CPDC entered into a commercial sublicense agreement with Lawson Health Research Institute. This allows Lawson to utilize [18F]PSMA-1007 for clinical studies involving participants in the London, Ontario region, further supporting research and potentially patient access programs.][44]

These licensing agreements illustrate the collaborative network required to advance a radiopharmaceutical from its initial discovery to widespread clinical application, involving academic centers, specialized radiopharmaceutical companies, and research institutes. Such agreements define the rights and responsibilities for development, manufacturing, regulatory submissions, and commercial distribution in specific territories.

C. Global Regulatory Status and Approved Indications

The regulatory status of 18F-PSMA-1007 varies across different global regions, with distinct approvals for specific branded products containing this active substance. It is essential to differentiate between the general compound "18F-PSMA-1007" and specific drug products that have undergone regulatory review and approval.

Table 2: Global Regulatory Status and Approved Indications of 18F-PSMA-1007 (and its branded versions like Radelumin)

Region/Authority	Branded Name (if applicable)	Approval Status	Specifically Approved Adult Indications for 18F-PSMA-1007 Based Products	Snippet Source(s)
USA (FDA)	Not explicitly stated as "18F-PSMA-1007"	No direct FDA approval for "18F-PSMA-1007" as a distinct entity is mentioned. Other 18F-PSMA agents (Pylarify, Posluma) are approved.	N/A for "18F-PSMA-1007" based on provided snippets. Pylarify & Posluma: PET imaging of PSMA-positive lesions in men with PCa (suspected metastasis for initial definitive therapy; suspected recurrence based on elevated PSA).	45
Europe (EMA & National)	Radelumin	Approved in France (Dec 2021), Germany, Switzerland (Posimed Radiopharm AG), and other EU countries. EMA Paediatric Waiver granted.	Radelumin: Detection of PSMA-positive lesions with PET in adults with prostate cancer (PCa) in clinical settings such as: Primary staging of patients with high-risk PCa prior to primary curative therapy. Localization of recurrence in patients with suspected recurrence based on increasing serum PSA levels after primary curative intent therapy (indication varies slightly by national approval, e.g., France also includes detection of recurrence).	17
Canada (Health Canada)	N/A (Investigational)	Phase 3 trial completed by CPDC; submission to Health Canada anticipated. Not yet approved.	Investigational: Diagnosis of recurrent prostate cancer.	43
Australia (TGA)	N/A	No direct TGA approval for 18F-PSMA-1007 mentioned. Illuccix (68Ga-PSMA-11) is TGA approved.	N/A for 18F-PSMA-1007.	53
South Korea	뉴큐어엠라델루민주사액 (NewCureM Radelumin Inj.)	Approved (10 Dec 2024)	Prostatic Cancer.	14
United Kingdom (MHRA)	Radelumin	Marketing Authorisation PL 27959/0001 (ABX advanced biochemical compounds).	Detection of PSMA-positive lesions with PET in adults with PCa (Primary staging of high-risk PCa prior to initial curative therapy; To localize recurrence of PCa in patients with suspected recurrence based on increasing serum PSA levels after primary treatment with curative intent).	20

1. FDA (U.S. Food and Drug Administration)

The provided research materials do not contain explicit information confirming FDA approval for a product specifically identified as "18F-PSMA-1007" under that developmental code or name.45 Instead, the FDA has granted approval to other 18F-labeled PSMA PET imaging agents. These include:

• Pylarify (piflufolastat F 18)[: Approved in May 2021 for PET imaging of PSMA-positive lesions in men with prostate cancer. Its indications cover patients with suspected metastasis who are candidates for initial definitive therapy and patients with suspected recurrence based on elevated serum PSA levels.][45]
• Posluma (flotufolastat F18, formerly known as 18F-rhPSMA-7.3)[: Approved in May 2023 for similar indications as Pylarify.][45][ Gallium-68 PSMA-11 (Illucix, Locametz) also holds FDA approval for prostate cancer imaging.][45] The absence of a direct mention of FDA approval for "18F-PSMA-1007" suggests that, if used in the United States, it would likely be under an Investigational New Drug (IND) application for clinical trials or other research purposes, rather than as a commercially marketed and FDA-approved drug under this specific identifier. The FDA's approval process for PSMA PET agents has focused on specific drug products backed by comprehensive New Drug Applications (NDAs) that include extensive clinical trial data, such as those for Pylarify and Posluma.

2. EMA (European Medicines Agency) and European National Approvals

In Europe, 18F-PSMA-1007 has achieved regulatory approval in several countries, marketed under the brand name Radelumin by ABX advanced biochemical compounds GmbH or its partners like Posimed Radiopharm AG.17

• France[: Marketing authorization for Radelumin was granted at the end of 2021.][28][ The Haute Autorité de Santé (HAS) issued a favorable opinion for reimbursement for the primary staging of patients with high-risk PCa prior to primary curative therapy.][17]
• Germany and other EU countries[: Radelumin has also received marketing authorization in Germany, with production and marketing in additional European countries commencing or planned.][24]
• Switzerland[: Radelumin is authorized by Swissmedic, with Posimed Radiopharm AG as the Marketing Authorization Holder. The approved indication is for imaging PSMA-positive lesions by PET in adult patients with prostate cancer.][19]
• United Kingdom (MHRA)[: Radelumin holds a UK marketing authorisation (PL 27959/0001) issued to ABX advanced biochemical compounds GmbH. The approved indications are for the detection of PSMA-positive lesions with PET in adults with PCa, specifically for primary staging of high-risk PCa prior to initial curative therapy, and to localize recurrence of PCa in patients with suspected recurrence based on increasing serum PSA levels after primary treatment with curative intent.][20]
• EMA Paediatric Waiver[: The EMA granted a product-specific waiver (EMEA-003250-PIP01-22) for fluorine (18F) PSMA-1007 (applicant: BIOKOSMOS S.A.) from the obligation to conduct studies in the paediatric population for the "Visualisation of prostate specific membrane antigen in prostate cancer." This waiver was granted because the condition for which the medicinal product is intended occurs only in adult populations.][33]

[The European Public Assessment Report (EPAR) for Radelumin, which would contain detailed information about its assessment by the EMA or national competent authorities through mutual recognition or decentralized procedures, is referenced as being available on the EMA website.][19] The approval of Radelumin in these European nations signifies its established clinical role and acceptance by regulatory bodies for specific adult prostate cancer imaging indications.

3. Health Canada

The Centre for Probe Development and Commercialization (CPDC) has been actively developing [18F]PSMA-1007 for the Canadian market. A Phase 3 clinical trial (CPD-002) evaluating its use in men with suspected persistent or recurrent prostate cancer has been completed (or closed).43 CPDC announced its intention to submit the trial results to Health Canada for regulatory review.43 As of the information available in the snippets, explicit approval by Health Canada has not yet been granted, but the agent is in advanced stages of regulatory consideration.51

4. TGA (Australia)

The provided materials primarily discuss the Therapeutic Goods Administration (TGA) approval of Illuccix (68Ga-PSMA-11) in Australia.53 While 18F-PSMA-1007 is mentioned in comparative contexts within Australian assessments (e.g., MSAC application 1632, which noted preliminary evidence suggesting non-inferiority to 68Ga-PSMA-11 53), there is no direct statement within the snippets confirming TGA approval for 18F-PSMA-1007 itself.

5. Other Regions

• South Korea[: 18F-PSMA-1007, under the name 뉴큐어엠라델루민주사액 (NewCureM Radelumin Inj.), was approved on December 10, 2024, for use in Prostatic Cancer.][14]

This diverse regulatory landscape underscores the complex process of bringing novel radiopharmaceuticals to global markets, with approvals often being country- or region-specific and tied to particular branded products and their supporting clinical data.

V. Pharmacokinetics and Biodistribution

A. Absorption and Distribution in Normal Tissues

Following intravenous administration, 18F-PSMA-1007 exhibits a characteristic biodistribution pattern, with physiological uptake observed in several normal organs known to express PSMA or involved in its clearance. These include:

• Salivary glands (parotid, submandibular)[: Consistent and often high uptake.][4]
• Lacrimal glands[: Notable uptake is also seen.][39]
• Liver[: Significant uptake due to its primary role in the hepatobiliary excretion of the tracer.][4]
• Spleen[: Physiological uptake is observed.][4]
• Kidneys[: Uptake is present, though typically less intense than tracers with primary renal excretion.][4]
• Intestines (especially small intestine, gallbladder)[: Activity is seen due to hepatobiliary clearance.][4]
• Urinary bladder[: Generally shows low activity due to minimal renal excretion, which is a key characteristic of 18F-PSMA-1007.][3]
• Blood pool[: Activity in the blood pool clears relatively rapidly.][39]
• Other sites[: Uptake can also be seen in sympathetic ganglia (e.g., celiac, stellate).][4]

[Understanding this normal biodistribution pattern is critical for accurate PET image interpretation, allowing clinicians to differentiate physiological tracer accumulation from pathological uptake in cancerous lesions. The high uptake in the liver and gallbladder, a direct consequence of its hepatobiliary excretion pathway, is advantageous for clear visualization of the pelvic region by minimizing bladder artifact. However, this same characteristic can present a challenge for the detection of PSMA-positive liver metastases, as tumor uptake may be masked by the high background activity in normal liver parenchyma.][4]

B. Uptake in Cancerous Tissues (Prostate cancer lesions, metastases)

[18F-PSMA-1007 demonstrates high and specific uptake in PSMA-expressing cancerous tissues, including primary prostate cancer lesions, involved regional lymph nodes, and distant metastases (e.g., in bone, soft tissues).][3][ This avid tumor uptake is fundamental to its diagnostic utility. Good tumor-to-background ratios are generally observed, and these ratios often improve at later imaging time points (e.g., 2-3 hours post-injection) as background activity clears while the tracer is retained in tumor cells, partly due to internalization.][3][ Quantitative parameters, such as the Standardized Uptake Value (SUV), are used to measure the intensity of tracer accumulation in lesions.][40]

C. Routes and Rate of Excretion (Emphasis on hepatobiliary vs. urinary clearance)

[A distinguishing pharmacokinetic feature of 18F-PSMA-1007 is its primary route of excretion via the hepatobiliary system.][3][ This means the tracer is predominantly cleared from the body through the liver and bile, subsequently entering the intestines. Consequently, renal excretion of 18F-PSMA-1007 is minimal. Studies have reported very low percentages of the injected activity being eliminated in the urine; for example, one study found an average of only 1.2% excreted in the first 0-2 hours post-injection ][39][, and another reported approximately 8% of injected activity in urine over 20 hours.][41][ The clearance kinetics of 18F-PSMA-1007 are noted to be somewhat slower than those of 68Ga-PSMA-11.][6]

[This hepatobiliary clearance pathway is a significant advantage, particularly for imaging the pelvic region, including the prostate bed (for local recurrence) and pelvic lymph nodes. By minimizing the accumulation of radioactivity in the urinary bladder, 18F-PSMA-1007 reduces the potential for intense bladder activity to obscure adjacent pathological lesions, a common challenge with PSMA tracers that are primarily excreted renally.][3][ However, it is important to note that while generally low, "inconsistent urinary excretion patterns" or "inconsistent high urinary uptake" have been observed in a subset of patients (up to 32.4% in one report).][1] The reasons for this variability are not fully elucidated but suggest that while the average urinary excretion is low, individual patient differences can occasionally diminish this key advantage in some cases.

D. Optimal Uptake Times for Imaging

[The optimal time window for acquiring PET images after the administration of 18F-PSMA-1007 typically ranges from 90 to 120 minutes post-injection.][18][ This timeframe allows for sufficient tracer accumulation in PSMA-positive lesions and adequate clearance from background tissues, leading to favorable tumor-to-background contrast. Some studies indicate that good tumor-to-background ratios can be observed 2 to 3 hours post-injection, and these ratios may continue to improve at these later time points.][4]

[While some investigations have explored earlier imaging, for instance, starting scans at 60 minutes post-injection with comparable performance in certain contexts like primary staging ][4][, the generally slower clearance kinetics of 18F-PSMA-1007 compared to agents like 68Ga-PSMA-11 often support the utility of later imaging times.][4] The choice of the specific uptake period can be influenced by institutional protocols and the specific clinical question being addressed. The longer physical half-life of 18F (approximately 110 minutes) makes these extended uptake periods logistically feasible, unlike tracers with shorter half-lives. Standardizing the uptake time is crucial for ensuring consistency and comparability of imaging results, particularly in longitudinal studies or multi-center trials.

E. Blood-Brain Barrier Penetration

[Current evidence indicates that 18F-PSMA-1007 does not significantly cross the intact blood-brain barrier (BBB).][4][ This characteristic limits its direct utility for imaging primary brain tumors or metastases within the brain parenchyma unless the BBB is disrupted. However, this is generally not a limitation for its primary applications in prostate cancer staging and restaging, as brain metastases are less common at initial diagnosis or early recurrence. It is noteworthy that PSMA is also known as glutamate carboxypeptidase II (GCPII) in the brain, and 18F-PSMA-1007 has been used for autoradiographic investigations of GCPII expression in brain tissue ex vivo or in specific research settings, distinct from in vivo clinical brain imaging for cancer detection.][4]

VI. Clinical Applications in Prostate Cancer Imaging

A. Initial Staging of High-Risk Prostate Cancer

[18F-PSMA-1007 PET/CT has demonstrated considerable utility in the initial staging of patients with high-risk prostate cancer. Numerous studies report its superior diagnostic accuracy and sensitivity compared to conventional imaging modalities such as CT, MRI, and whole-body bone scans, as well as some other radiotracers.][1][ It is particularly effective in detecting pelvic and locoregional disease, including small lymph node metastases and early bone lesions that may not be apparent on conventional imaging techniques.][1][ This enhanced detection capability can lead to a more accurate initial staging, often resulting in the upstaging of disease compared to assessments based solely on traditional methods.][3][ For instance, in locoregional staging, 18F-PSMA-1007 PET/CT has shown improved accuracy over MRI for determining the pathological T stage, identifying the dominant intraprostatic nodule, assessing laterality, and detecting extracapsular extension.][58]

[Accurate initial staging is fundamental for determining the most appropriate primary treatment strategy—such as radical prostatectomy, radiation therapy, or systemic therapy—and for predicting patient prognosis. Under-staging, which can occur with conventional imaging due to its lower sensitivity for small-volume disease, may lead to sub-optimal treatment choices, potentially compromising curative intent. The superior performance of 18F-PSMA-1007 PET/CT in providing a more comprehensive assessment of disease extent, particularly for N (nodal) and M (metastatic) staging in high-risk patients, suggests its potential role as a primary imaging modality in this setting. It may replace or effectively complement conventional imaging, offering the advantage of whole-body staging in a single examination, which can improve diagnostic efficiency and patient convenience, and ultimately lead to more informed and potentially more effective treatment planning.][1]

B. Detection of Biochemical Recurrence (especially at low PSA levels)

[One of the most significant clinical applications of 18F-PSMA-1007 PET/CT is in the detection of disease recurrence in patients who experience biochemical recurrence (BCR) following definitive primary therapy (e.g., radical prostatectomy or radiation therapy). BCR is characterized by a rising PSA level in the absence of clinically or radiologically evident disease by conventional imaging. 18F-PSMA-1007 PET/CT has proven highly effective in localizing the sites of recurrence in this challenging scenario, demonstrating notable detection rates even at very low PSA levels (e.g., ≤ 0.5 ng/mL) where traditional imaging modalities often fail.][1]

[The detection rates of 18F-PSMA-1007 PET/CT generally increase with rising PSA levels; however, its ability to identify recurrent lesions (local recurrence in the prostate bed, pelvic lymph node metastases, or distant metastases) at low PSA thresholds is a key advantage.][3][ For example, detection rates of around 50% have been reported for PSA levels between 0.2–0.5 µg/L, increasing substantially at higher PSA concentrations.][3] This early localization of recurrence is crucial for guiding salvage therapies, such as salvage radiation therapy to the prostate bed or pelvic nodes, or targeted ablation of oligometastatic lesions. By precisely identifying the location and extent of recurrent disease when the tumor burden is still relatively small, 18F-PSMA-1007 PET/CT enables clinicians to offer timely and targeted interventions. This approach holds the potential to improve oncological outcomes, possibly delaying the need for systemic therapies, which are often associated with greater side effects, or rendering salvage treatments more effective than if applied blindly or based on less sensitive imaging.

C. Role in Guiding Therapeutic Decisions

The information provided by 18F-PSMA-1007 PET/CT frequently plays a pivotal role in guiding therapeutic decisions for patients with prostate cancer across various stages of the disease.1 By offering a more accurate assessment of disease extent, it can lead to significant modifications in treatment planning.

In the context of initial staging, particularly for high-risk patients, 18F-PSMA-1007 PET/CT can identify previously occult metastatic disease, thereby altering the treatment intent from curative local therapy to systemic treatment or a combination approach. Conversely, it can confirm genuinely localized disease, supporting the use of definitive local therapies like surgery or radiation.

[For patients with biochemical recurrence, the ability of 18F-PSMA-1007 PET/CT to pinpoint the location(s) of recurrence is critical for selecting appropriate salvage strategies.][1] If recurrence is confined to the prostate bed or regional lymph nodes, targeted salvage radiotherapy may be employed. If oligometastatic disease (a limited number of metastases) is detected, metastasis-directed therapies such as stereotactic body radiation therapy (SBRT) or salvage lymph node dissection might be considered. The detection of widespread metastatic disease would typically prompt a shift towards systemic therapies.

[Furthermore, while not its primary established role in the provided snippets, the quantitative uptake of PSMA tracers (like SUV values) is an area of active research for predicting response to PSMA-targeted radioligand therapies (RLT), such as those using Lutetium-177 (177Lu) labeled PSMA ligands. Although this is more directly established for theranostic pairs like 68Ga-PSMA-11/177Lu-PSMA-617, 18F-PSMA-1007 imaging could potentially aid in patient selection for such therapies by confirming PSMA expression in tumor lesions.][11][ The structural and conceptual links between 18F-PSMA-1007 and theranostic compounds like PSMA-617 ][4] hint at its supportive role in the broader PSMA-targeted theranostic landscape, at minimum by identifying patients whose tumors express the target.

VII. Diagnostic Performance

A. Overall Diagnostic Accuracy, Sensitivity, and Specificity

[18F-PSMA-1007 PET/CT has consistently demonstrated superior overall diagnostic accuracy and sensitivity in both the initial staging of prostate cancer and the detection of recurrent disease when compared to conventional imaging modalities.][1][ Its strength lies in identifying PSMA-positive lesions throughout the body. For instance, in the context of lymph node staging, one study reported a lesion-based sensitivity of 81.7% and an exceptionally high specificity of 99.6% for detecting metastatic lymph nodes larger than 3 mm.][5][ When all malignant nodes regardless of size were considered, the sensitivity was 71.2% with a specificity of 99.5%.][5][ Patient-based analyses also showed high sensitivity (85.9% for nodes >3mm) and specificity (99.5%).][5]

[However, a significant limitation affecting its overall specificity profile is the issue of unspecific bone uptake (UBU), which can lead to false-positive interpretations for bone metastases.][1] This aspect will be discussed in more detail in Section X. High sensitivity is crucial for minimizing missed diagnoses, particularly of small-volume disease, while high specificity is vital to prevent over-treatment based on false-positive findings. The balance between these metrics, and the strategies to mitigate limitations, are key to its effective clinical use.

Table 3: Summary of Diagnostic Performance of 18F-PSMA-1007 in Prostate Cancer (Illustrative Examples)

Clinical Setting	Comparator	Key Performance Metric	Reported Value(s)	Snippet Source(s)
Initial Staging (Overall)	Conventional Imaging	Diagnostic Accuracy, Sensitivity	Superior	1
Initial Staging (Locoregional - T stage)	MRI	Accuracy	45% (18F-PSMA-1007) vs 28% (MRI) (P=0.003)	58
Initial Staging (Dominant Nodule ID)	MRI	Accuracy	94% (18F-PSMA-1007) vs 83% (MRI) (P=0.007)	58
Lymph Node Staging (Lesion-based, >3mm)	Histopathology	Sensitivity	81.7%	5
		Specificity	99.6%	5
		PPV	92.4%	5
		NPV	98.9%	5
Lymph Node Staging (Patient-based, >3mm)	Histopathology	Sensitivity	85.9%	5
		Specificity	99.5%	5
Biochemical Recurrence (Overall)	18F-Fluorocholine PET/CT	Detection Rate	Superior for 18F-PSMA-1007 (Overall: 0.82 vs 0.65)	12
Biochemical Recurrence (PSA <0.5 ng/mL)	SOT (Standard of Truth)	Detection Rate	57% (18F-PSMA-1007) vs 39% (18F-Fluorocholine)	12
Biochemical Recurrence (PSA 0.2-0.5 µg/L)	N/A	Detection Rate	~50%	3
Biochemical Recurrence (Low PSA, PET/MR)	12-month Follow-up	Detection Rate (PSA 0.1-0.5 ng/mL)	75% (45/60 patients)	13

Note: Performance metrics can vary based on study design, patient population, PSA levels, and definition of reference standard. This table provides illustrative examples from the provided snippets.

B. Performance in Lymph Node Staging

[18F-PSMA-1007 PET/CT has demonstrated high performance in the detection of lymph node metastases in prostate cancer patients. Studies utilizing histopathological correlation have shown that it can reliably identify malignant lymph nodes with exceptional specificity, often exceeding 99%.][5] This high specificity is crucial as it minimizes the likelihood of false-positive findings, which could lead to unnecessary lymph node dissections or inappropriate treatment planning.

[The sensitivity for detecting metastatic lymph nodes varies depending on factors such as the size of the nodes and the clinical setting (primary staging vs. biochemical recurrence). For lymph nodes larger than 3 mm, lesion-based sensitivity has been reported at 81.7%, and patient-based sensitivity at 85.9%.][5][ When all malignant nodes, irrespective of size, are considered, the sensitivity is somewhat lower (e.g., 71.2% lesion-based) ][5][, reflecting the inherent challenge of detecting very small metastatic deposits. Despite this, its ability to detect nodal metastases often surpasses that of conventional imaging modalities like CT and MRI, which rely primarily on size criteria and morphological changes that are less sensitive for small or normal-sized involved nodes. The low urinary excretion of 18F-PSMA-1007 is particularly advantageous for assessing pelvic lymph nodes, as it reduces interference from bladder activity.][5]

C. Comparison with Conventional Imaging Modalities (CT, MRI, Bone Scan)

[18F-PSMA-1007 PET/CT has consistently shown superior diagnostic performance when compared to conventional imaging modalities—namely computed tomography (CT), magnetic resonance imaging (MRI), and whole-body bone scintigraphy (WBBS)—for both the initial staging of prostate cancer and the detection of recurrent disease.][1] This superiority is particularly evident in its ability to identify small-volume disease, detect metastases at lower PSA levels in the biochemical recurrence setting, and provide a comprehensive whole-body assessment in a single imaging session.

[In the context of initial staging, especially for high-risk patients, 18F-PSMA-1007 PET/CT can detect lymph node metastases and distant metastases (including early bone lesions) that are often missed by CT, MRI, or WBBS due to their reliance on morphological changes or size criteria.][3][ For instance, a direct comparison with MRI for locoregional staging demonstrated that 18F-PSMA-1007 PET/CT had significantly higher accuracy in correctly identifying the final pathological T stage (45% vs. 28%), the dominant intraprostatic nodule (94% vs. 83%), tumor laterality (64% vs. 44%), and extracapsular extension (75% vs. 63%).][58]

[For detecting biochemical recurrence, conventional imaging often fails to localize disease when PSA levels are low. 18F-PSMA-1007 PET/CT, however, shows significantly higher detection rates in this scenario.][1][ The ability of 18F-PSMA-1007 PET/CT to provide a comprehensive, whole-body staging assessment (evaluating soft tissues, lymph nodes, and bone simultaneously) in a single session presents a notable advantage over the traditional multi-modal approach, which typically involves separate CT or MRI scans for soft tissue and nodal assessment, plus a bone scan for skeletal evaluation.][52] This integrated approach can improve patient convenience, reduce the time to complete staging, and potentially lead to more accurate and timely treatment decisions.

D. Comparative Efficacy with Other PSMA-PET Tracers (e.g., 68Ga-PSMA-11, 18F-DCFPyL)

The landscape of PSMA-PET imaging includes several radiotracers, with 68Ga-PSMA-11 and other 18F-labeled agents like 18F-DCFPyL being prominent comparators to 18F-PSMA-1007.

• [Versus 68Ga-PSMA-11:] Numerous studies have compared 18F-PSMA-1007 with 68Ga-PSMA-11. Generally, 18F-PSMA-1007 demonstrates comparable or, in some instances, slightly higher sensitivity for detecting recurrent prostate cancer lesions.4 A key advantage of 18F-PSMA-1007 is its significantly lower urinary excretion due to its primary hepatobiliary clearance. This results in reduced activity in the urinary bladder, facilitating better detection of local recurrences in the prostate bed and metastases in pelvic lymph nodes adjacent to the urinary tract.5 However, this hepatobiliary excretion leads to higher physiological uptake in the liver and gallbladder, which can sometimes complicate the assessment of lesions in these areas. A notable drawback of 18F-PSMA-1007 compared to 68Ga-PSMA-11 is a higher incidence of unspecific bone uptake (UBU), which can lead to equivocal findings or potential false positives for bone metastases if not interpreted cautiously with anatomical correlation.8 The longer half-life and potential for higher production yields with 18F also offer logistical advantages for 18F-PSMA-1007 over generator-produced 68Ga-PSMA-11.
• [Versus 18F-DCFPyL:] Direct head-to-head comparisons between 18F-PSMA-1007 and 18F-DCFPyL are less numerous in the provided materials, but some differences are highlighted. 18F-DCFPyL, another 18F-labeled PSMA tracer, generally shows higher renal excretion compared to 18F-PSMA-1007, which can lead to greater bladder activity similar to 68Ga-PSMA-11.7 Conversely, some evidence suggests that 18F-DCFPyL may exhibit fewer equivocal or unspecific bone lesions and potentially higher inter-reader agreement for assessing skeletal findings compared to 18F-PSMA-1007.55 18F-DCFPyL has also been described as more reproducible for the identification of lymph nodes in some contexts.55 The choice between these 18F-labeled agents may therefore depend on the specific clinical question; for instance, 18F-PSMA-1007 might be preferred if pelvic recurrence near the bladder is highly suspected, while 18F-DCFPyL might be favored if bone specificity is a primary concern.

The decision between different PSMA tracers is multifaceted, influenced by factors such as local availability, cost-effectiveness, the specific clinical scenario (e.g., primary staging vs. BCR, suspected site of recurrence), and a thorough understanding of the unique biodistribution patterns, advantages, and limitations of each agent. While 18F-PSMA-1007's low urinary excretion offers a distinct benefit for pelvic imaging over tracers with significant renal clearance, its propensity for higher UBU represents a critical trade-off that necessitates careful image interpretation, often requiring correlation with CT or MRI findings and clinical data to ensure diagnostic accuracy. No single PSMA tracer is universally superior across all performance metrics and clinical situations; thus, the selection requires a nuanced consideration of these factors.

VIII. Imaging Protocol and Patient Management

A. Patient Preparation Guidelines (Hydration, fasting, voiding, medication adjustments)

Proper patient preparation is essential for optimizing the quality of 18F-PSMA-1007 PET/CT scans and ensuring patient safety. General guidelines include:

• Fasting[: Fasting is typically not required for 18F-PSMA-1007 PET imaging.][18] Patients can usually maintain their normal diet.
• Hydration[: Adequate hydration is generally recommended. Patients may be encouraged to drink a sufficient amount of water before the scan.][18] While 18F-PSMA-1007 is primarily hepatobiliary excreted, good hydration can help facilitate the clearance of any minor renally excreted fraction and contributes to overall patient well-being and radiation safety by promoting more frequent voiding post-injection.
• Voiding[: Patients are usually advised to empty their bladder immediately before the PET scan acquisition and frequently during the initial hours following image acquisition.][18] This practice helps to minimize radiation exposure to the bladder wall, even though bladder activity from 18F-PSMA-1007 is typically low.
• Medication Adjustments[: Patients can generally continue taking most of their regular medications.][18][ However, it is important to note that the initiation of Androgen Deprivation Therapy (ADT) shortly before a PSMA PET scan might lead to decreased PSMA expression and consequently lower tracer uptake in tumor lesions. Therefore, if clinically feasible, PSMA-ligand PET/CT should be performed before the onset of new ADT.][36][ A recent history of prostate cancer-specific medications and treatments should be provided for proper scan interpretation.][18]
• Other Preparations[: Patients should avoid strenuous physical exercise for 24 hours prior to the appointment, as this can sometimes lead to muscle uptake of PET tracers, although this is less of a concern for PSMA-specific agents compared to FDG.][66][ Patients should wear comfortable clothing and remove jewelry or metal objects that could interfere with imaging.][66]

The emphasis on hydration and frequent voiding, while standard for many PET procedures to reduce radiation dose, serves primarily radiation safety goals with 18F-PSMA-1007 rather than artifact reduction in the pelvis, given its predominant hepatobiliary excretion.

B. Administration Route and Recommended Dosage/Injected Activity

[18F-PSMA-1007 is administered via an intravenous (IV) bolus injection.][18][ The recommended injected activity is typically weight-based, commonly in the range of 3 to 4 MBq per kilogram (MBq/kg) of body weight.][18][ For example, the Radelumin Summary of Product Characteristics (SmPC) suggests a dosage of 3.6-4.4 MBq/kg.][18][ This often translates to a total injected activity of approximately 210–308 MBq (around 5.7–8.3 mCi) for an average-weight adult (e.g., 70 kg), with maximum administered activities often capped around 400-450 MBq to manage radiation exposure.][20][ The precise dose can vary based on institutional protocols and equipment sensitivity. After injection, the syringe should be flushed with saline to ensure the full dose is administered.][36]

C. PET/CT (or PET/MRI) Acquisition Parameters

[Standardized acquisition protocols are crucial for obtaining high-quality and interpretable 18F-PSMA-1007 PET images. These protocols are often guided by joint EANM/SNMMI procedure guidelines for PSMA PET/CT imaging.][36]

Table 5: Recommended Patient Preparation and 18F-PSMA-1007 PET/CT Imaging Protocol Parameters

Phase	Parameter	Recommendation/Typical Value	Snippet Source(s)
Patient Preparation	Fasting	Generally not required	18
	Hydration	Adequate hydration encouraged	18
	Voiding	Immediately before scan acquisition and frequently post-injection	18
	Medication Adjustment	Continue most medications; perform scan before new ADT if possible	18
	Exercise	Avoid strenuous exercise 24h prior	66
Administration	Route	Intravenous (IV) bolus injection	18
	Injected Activity	3-4 MBq/kg (or 3.6-4.4 MBq/kg); max ~400-450 MBq	18
Imaging	Uptake Time (Injection to Scan Start)	90-120 minutes (optimal); 60 min possible, 2-3h for best tumor-to-background	4
	Patient Positioning	Supine, arms elevated above head if tolerated	36
	Scan Range (PET & CT)	Typically vertex to mid-thigh	20
	CT Acquisition	Low-dose CT for attenuation correction & anatomical localization. Diagnostic CT (with/without contrast) may be performed per institutional protocol.	36
	PET Acquisition Mode	3D mode	36
	PET Scan Duration per Bed Position	Typically 1-4 minutes (or equivalent for continuous table motion), adjusted for activity	36
	PET Image Reconstruction	Iterative algorithms (e.g., OSEM), with corrections for attenuation, scatter, randoms. PSF correction may be used. Reconstruct with and without attenuation correction.	4

[For ]PET/CT imaging:

• Uptake Period[: Imaging typically commences 90 to 120 minutes after the intravenous injection of 18F-PSMA-1007.][18]
• Patient Positioning[: The patient is positioned supine on the scanner bed, usually with arms raised above the head if tolerated, to minimize artifacts and allow for an unobstructed view of the torso.][36]
• CT Scan[: A low-dose CT scan is acquired first, typically from the vertex of the skull to the mid-thigh. This CT data is used for attenuation correction of the subsequent PET emission data and for anatomical localization of PET findings. Diagnostic quality CT scans, potentially with intravenous and/or oral contrast, may be performed depending on institutional protocols and clinical indications.][36]
• PET Scan[: The PET emission scan covers the same anatomical range as the CT scan, typically acquired in 3D mode. Acquisition usually starts from the mid-thigh and proceeds cranially. The scan duration per bed position is generally 1 to 4 minutes, adjusted based on factors like injected activity, patient weight, and scanner sensitivity.][36]
• Image Reconstruction[: PET images are reconstructed using iterative algorithms, such as Ordered Subsets Expectation Maximization (OSEM). Standard corrections for physical factors like attenuation (using the CT data), scatter, and random coincidences are applied. Point Spread Function (PSF) modeling may also be incorporated to improve image resolution. It is recommended to reconstruct images both with and without attenuation correction to help identify potential artifacts.][4]

For PET/MRI imaging:

18F-PSMA-1007 can also be used with PET/MRI systems. This hybrid modality offers the molecular information from PET combined with the superior soft-tissue contrast of MRI, which can be particularly advantageous for evaluating local recurrence in the prostate bed and pelvic soft tissues.13 While detailed PET/MRI acquisition parameters are outside the scope of the general PSMA PET/CT guidelines referenced 36, the fundamental principles of tracer administration and uptake times would be similar, with MRI sequences tailored to the clinical question. The synergistic information from simultaneous PET and multiparametric MRI assessment of pelvic lesions is of particular benefit in early BCR.13

Adherence to these standardized protocols is vital for ensuring high-quality, reproducible imaging results, which are essential for accurate diagnosis, staging, and monitoring of prostate cancer patients.

IX. Safety Profile

A. Reported Adverse Events and Overall Tolerability from Clinical Trials

[Based on the available clinical trial data and post-marketing experience, 18F-PSMA-1007 is generally reported to be well-tolerated by patients.][7][ The Radelumin Summary of Product Characteristics (SmPC) states that no undesirable effects have been reported to date from its evaluation in 191 patients in the ABX-CT-301 study and from over 1000 patients in published literature.][20][ Similarly, a preliminary safety assessment of the NCT04102553 trial involving 191 patients who underwent [18F]PSMA-1007 PET/CT found six contemporaneous adverse events, none of which were deemed related to the study drug by the investigator, and no serious adverse events were reported.][62]

[In another study focusing on 18F-rhPSMA-7.3 (a different PSMA ligand, but illustrative of the class), only one adverse event (mild headache, not requiring medication) was considered possibly related out of the patient cohort.][7][ Clinical trial information for 18F-PSMA-1007 (NCT05520255) includes screening for adverse effects immediately post-injection, immediately after the scan (approx. 2.5 hours post-injection), and self-reporting for delayed adverse events (1-7 days post-injection).][72][ Exclusion criteria for some trials include known allergies or sensitivity to any component of the investigational product.][63][ The main risk associated with diagnostic radiopharmaceuticals like 18F-PSMA-1007 is typically related to radiation exposure rather than direct pharmacological effects, given the very small (tracer) mass of the ligand administered. The Radelumin SmPC notes the theoretical risk of hypersensitivity reactions to the active substance or any of its excipients.][20]

B. Radiation Dosimetry: Effective Dose and Critical Organ Doses

The administration of 18F-PSMA-1007 results in radiation exposure to the patient. Dosimetry studies have been conducted to quantify this exposure.

The effective dose coefficient for 18F-PSMA-1007 has been reported as approximately 22-25 µSv/MBq.41 For a typical administered activity (e.g., 3-4 MBq/kg for an 80 kg patient, equating to 240-320 MBq, or a maximum recommended activity of 450 MBq), the total effective dose to the patient is estimated to be in the range of 4.4 to 8.6 mSv.6 This level of radiation exposure is comparable to other common diagnostic PET procedures and is generally considered acceptable within the context of the diagnostic benefits provided for cancer patients.

The organs receiving the highest absorbed radiation doses are typically those with significant physiological PSMA expression or those involved in the tracer's clearance pathway. For 18F-PSMA-1007, these critical organs include:

• Lacrimal glands[: Reported with absorbed dose coefficients as high as 98 µGy/MBq.][41]
• Kidneys[: Consistently among the organs with high uptake, with absorbed dose coefficients around 84.5 - 170 µGy/MBq (variations likely due to different calculation models or patient cohorts).][6]
• Salivary glands (parotid and submandibular)[: High uptake leads to significant absorbed doses, e.g., ~75-90 µGy/MBq.][6]
• Liver[: Due to hepatobiliary excretion, the liver receives a notable dose, around 60-70 µGy/MBq.][6]
• Spleen[: Also shows considerable uptake, with absorbed doses around 66-74 µGy/MBq.][6][ Other organs like the urinary bladder wall receive a lower dose compared to renally excreted PSMA tracers, owing to 18F-PSMA-1007's primary hepatobiliary clearance.][39][ The red marrow dose is also an important consideration in dosimetry.][39]

Understanding these critical organ doses is essential for the ALARA (As Low As Reasonably Achievable) principle in nuclear medicine, ensuring that the diagnostic benefits outweigh the potential radiation risks. The pattern of organ doses reinforces the importance of recognizing normal biodistribution to avoid misinterpreting physiological uptake as pathological.

Table 4: Radiation Dosimetry for 18F-PSMA-1007 (Representative Values)

Parameter / Organ	Absorbed Dose Coefficient (µGy/MBq) or Effective Dose	Snippet Source(s)
Effective Dose Coefficient	22 - 25 µSv/MBq	41
Effective Dose (typical scan)	4.4 - 8.6 mSv (for 200-450 MBq or 3-4 MBq/kg)	20
Critical Organs (Absorbed Dose Coefficient, µGy/MBq):
Lacrimal Glands	~98	41
Kidneys	~85 - 170	6
Salivary Glands (Parotid/Submandibular)	~75 - 90	6
Liver	~60 - 70	6
Spleen	~66 - 74	6
Urinary Bladder Wall	Lower than renally excreted tracers 39	39
Red Marrow	~1.21E-02 mGy/MBq	39

Note: Dosimetry values can vary based on the patient population, calculation methodology (e.g., OLINDA/EXM, IDAC), and specific study parameters. Values are representative ranges from the provided snippets.

C. Contraindications, Warnings, and Precautions

[The primary contraindication listed for Radelumin ([18F]PSMA-1007) is hypersensitivity to the active substance ([18F]PSMA-1007) or to any of the excipients used in its formulation.][20]

General warnings and precautions associated with the use of 18F-PSMA-1007, typical for radiopharmaceuticals, include:

• Radiation Exposure[: Patients undergoing PET scans with 18F-PSMA-1007 are exposed to ionizing radiation. While the effective dose is generally considered acceptable for diagnostic purposes, it contributes to the patient's cumulative lifetime radiation exposure, which is associated with a potential increased risk of cancer.][20] Therefore, the procedure should only be performed when the diagnostic benefit outweighs this risk, adhering to ALARA principles.
• Image Interpretation Errors (Risk of Misdiagnosis)[: Accurate interpretation of PSMA PET images requires expertise and awareness of potential pitfalls. False-positive findings can occur due to physiological uptake in normal PSMA-expressing tissues (salivary glands, kidneys, liver, spleen, ganglia, etc.) or uptake in benign conditions (e.g., inflammation, fractures, Paget's disease of bone, fibrous dysplasia) and non-prostatic malignancies that may also express PSMA.][17][ Unspecific bone uptake (UBU) is a particular challenge with 18F-PSMA-1007. False-negative results can also occur, for example, in tumors with low or absent PSMA expression or in very small lesions below the resolution limit of the PET scanner. Clinical correlation with other imaging modalities (CT, MRI) and patient history is crucial.][19]
• Patient Preparation[: Adequate patient hydration and instructions for frequent bladder voiding post-injection are recommended to minimize radiation dose to the bladder and other organs, although less critical for bladder artifact with 18F-PSMA-1007 due to its primary hepatobiliary excretion.][18]
• Handling of Radiopharmaceuticals: Standard safety measures for handling radioactive materials must be followed by healthcare personnel to minimize their radiation exposure.
• Use in Specific Populations:
• Pregnancy and Lactation[: Radelumin is not indicated for use in women.][20] Radiopharmaceuticals are generally contraindicated or used with extreme caution during pregnancy and lactation due to potential harm to the fetus or nursing infant.
• Paediatric Use[: 18F-PSMA-1007 is intended for adult patients with prostate cancer. The EMA has granted a paediatric waiver on the grounds that prostate cancer (the indicated condition) occurs only in adult populations.][33]
• Renal/Hepatic Impairment: While no specific contraindications related to mild/moderate renal or hepatic impairment are consistently highlighted for 18F-PSMA-1007 itself, caution is generally advised for radiopharmaceuticals in patients with severe organ dysfunction as it may alter tracer pharmacokinetics and radiation dosimetry.

No specific warnings regarding drug interactions are prominently featured for 18F-PSMA-1007 in the provided snippets, beyond general considerations for any administered medication.

X. Limitations, Challenges, and Pitfalls

A. Unspecific Bone Uptake (UBU): Prevalence, characteristics, interpretation challenges, and potential reasons

One of the most significant limitations and interpretation challenges associated with 18F-PSMA-1007 PET/CT is the phenomenon of unspecific bone uptake (UBU).

• Prevalence[: UBU is frequently observed with 18F-PSMA-1007, with some studies reporting its presence in up to 72% of patients.][1][ This prevalence appears to be notably higher than that observed with other PSMA tracers like 68Ga-PSMA-11 or 18F-DCFPyL.][8]
• Characteristics[: UBU typically manifests as focal areas of mild-to-moderate tracer accumulation in bones (often with SUVmax < 10.0) that do not have clear correlative findings of metastasis on the corresponding CT images (e.g., no lytic or sclerotic lesions).][8][ Common sites for UBU include the ribs, spine, and pelvis.][26]
• Interpretation Challenges[: The presence of UBU significantly complicates image interpretation, as it can be difficult to differentiate these benign uptakes from true early bone metastases, especially small ones or those without evident morphological changes on CT. This leads to reduced specificity for detecting bone lesions and can result in false-positive readings, potentially leading to patient over-staging and inappropriate treatment decisions.][1][ Higher inter-reader variability in assessing bone lesions with 18F-PSMA-1007 has also been reported, partly due to UBU.][1]
• Potential Reasons: The exact cause of the increased UBU with 18F-PSMA-1007 remains unclear, but several hypotheses exist:
• Benign Bone and Bone Marrow Changes[: Histological confirmation of some UBU sites has revealed benign conditions such as Paget's disease, hyperplastic bone marrow, fibrous dysplasia, degenerative changes, and healing fractures.][26] However, the high prevalence of UBU suggests these specific conditions may not account for all cases.
• Osteoporosis-Related Remodeling[: It has been proposed that increased bone remodeling activity associated with conditions like osteoporosis might contribute to UBU.][26]
• Tracer-Specific Properties[: The differing chemical structures and pharmacokinetic properties of 18F-PSMA-1007 compared to other PSMA ligands might play a role.][26] Its higher lipophilicity or plasma protein binding could influence its interaction with bone marrow components or areas of active bone turnover.
• Free Fluoride[: The hypothesis that UBU is due to the presence of free [18F]fluoride (which is bone-seeking) has largely not been substantiated by quality control data of the radiopharmaceutical, which typically shows high radiochemical purity.][26]

[The high incidence of UBU with 18F-PSMA-1007 necessitates a careful, multi-modal approach to characterize bone lesions. Correlation with CT morphology is standard. In equivocal cases, additional imaging with MRI, a different PSMA tracer with lower UBU (if available), or follow-up scans may be required. In some instances, biopsy might be considered, though this is invasive. This challenge can offset some of the "one-stop-shop" appeal of PSMA PET if further investigations are frequently needed for bone findings. Research is ongoing to better understand UBU and develop improved interpretation criteria (e.g., using SUV thresholds, textural analysis, or dual-time-point imaging) to enhance diagnostic confidence.][8]

B. Inconsistent Urinary Excretion Patterns

[While a key marketed advantage of 18F-PSMA-1007 is its generally low urinary excretion due to predominant hepatobiliary clearance, this characteristic is not universally consistent across all patients. Several sources indicate that "inconsistent urinary excretion patterns" or "inconsistent high urinary uptake" can occur in a subset of individuals, with reports suggesting this might affect up to 32.4% of patients in some cohorts.][1]

When significant urinary activity is present in the bladder or ureters, it can obscure the visualization of adjacent pelvic structures, including the prostate bed (site of potential local recurrence) and regional lymph nodes. This can negate one of the primary intended benefits of 18F-PSMA-1007 over PSMA tracers that are primarily cleared via the renal route (e.g., 68Ga-PSMA-11, 18F-DCFPyL). The reasons for this inter-patient variability in urinary excretion are not fully understood from the provided materials but could be related to individual differences in metabolism, hydration status, or renal function, even if not severely impaired. This inconsistency is a recognized limitation that clinicians must be aware of when interpreting 18F-PSMA-1007 PET scans, particularly when evaluating the pelvis.

C. Inter-reader Variability

[Some studies have reported higher inter-reader variability in the interpretation of 18F-PSMA-1007 PET/CT images, particularly concerning the assessment of bone lesions.][1] This variability can be attributed, in part, to the challenges posed by unspecific bone uptake (UBU). Differentiating subtle UBU from early metastatic involvement can be subjective and may depend on the reader's experience and the interpretative criteria applied.

[High inter-reader variability can impact the reproducibility and reliability of diagnostic reports, potentially leading to inconsistencies in patient staging and management. To mitigate this, the development and consistent application of standardized interpretation criteria, such as PSMA-RADS (Reporting and Data System) or miPSMA (molecular imaging PSMA) scoring systems, are crucial.][26] Furthermore, specialized training and accumulated experience in reading 18F-PSMA-1007 scans, with a particular focus on recognizing patterns of UBU and other pitfalls, are essential for improving concordance among readers and ensuring accurate clinical reporting.

D. Other Potential Pitfalls in Image Interpretation

Beyond UBU and inconsistent urinary activity, other potential pitfalls in interpreting 18F-PSMA-1007 PET/CT images arise from the physiological uptake of the tracer in various normal tissues and its potential accumulation in certain benign or non-prostatic malignant conditions:

• Physiological Uptake[: As detailed in Section V.A, significant physiological uptake occurs in the salivary glands, lacrimal glands, liver, spleen, kidneys, intestines, and sympathetic ganglia (e.g., celiac, stellate ganglia).][4] Intense uptake in these organs is normal and must be distinguished from metastatic disease. For example, PSMA-avid ganglia can sometimes be mistaken for lymph node metastases if their typical anatomical locations and appearance are not recognized.
• Uptake in Benign Conditions[: PSMA expression and, consequently, 18F-PSMA-1007 uptake can be seen in various benign conditions. Apart from UBU related to degenerative changes or fractures, uptake has been reported in inflammatory lesions, Paget's disease of bone, fibrous dysplasia, and other non-malignant processes.][19]
• Uptake in Non-Prostatic Malignancies[: PSMA is expressed in the neovasculature of many solid tumors, and direct expression on tumor cells has also been reported for some non-prostatic cancers (e.g., hepatocellular carcinoma, renal cell carcinoma, glioblastoma, thyroid cancer, breast cancer).][4] Incidental detection of such tumors or misinterpretation of their PSMA uptake as prostate cancer metastases is possible if the clinical context and anatomical information from CT/MRI are not carefully considered.

Awareness of these potential pitfalls, thorough knowledge of 18F-PSMA-1007's normal biodistribution patterns, and careful correlation of PET findings with anatomical details from the co-registered CT (or MRI) and the patient's overall clinical picture are paramount for avoiding misdiagnosis and ensuring the accurate application of this imaging modality.

XI. Conclusion and Future Perspectives

A. Summary of 18F-PSMA-1007's Current Role in Prostate Cancer Management

[18F-PSMA-1007 PET/CT has emerged as a highly valuable diagnostic imaging tool in the management of prostate cancer. Its primary strength lies in its superior diagnostic accuracy and sensitivity for both the initial staging of high-risk prostate cancer and the detection of biochemical recurrence, particularly at low PSA levels, when compared to conventional imaging modalities like CT, MRI, and bone scintigraphy.][1][ A key distinguishing feature and advantage of 18F-PSMA-1007 is its predominantly hepatobiliary excretion, leading to low urinary bladder activity. This characteristic significantly enhances the visualization of the prostate bed and pelvic lymph nodes, areas often obscured by bladder signal with renally excreted PSMA tracers.][3][ The 18F label also offers logistical benefits, including a longer half-life (~110 minutes) suitable for centralized production and distribution, and potentially improved image resolution due to lower positron energy compared to 68Ga.][5]

[However, the clinical application of 18F-PSMA-1007 is not without limitations. The most significant challenge is the relatively high incidence of unspecific bone uptake (UBU), which can reduce specificity for bone metastases and lead to diagnostic ambiguity.][1][ Additionally, while generally low, inconsistent patterns of urinary excretion have been reported in a subset of patients, potentially diminishing its pelvic imaging advantage in those cases.][1][ Higher inter-reader variability, especially for bone lesions, also underscores the need for expertise and standardized interpretation.][1]

[Despite these limitations, 18F-PSMA-1007 significantly impacts patient management by enabling more precise staging, facilitating earlier detection of recurrence, and thereby allowing for more informed and tailored therapeutic decisions, including the planning of salvage therapies.][1] Its regulatory approval in several European countries (as Radelumin) and ongoing clinical development in regions like Canada attest to its recognized clinical value.

B. Ongoing Research and Potential Future Developments/Applications

The field of PSMA-targeted imaging, including the use of 18F-PSMA-1007, is dynamic and continues to evolve. Several avenues of ongoing research and potential future developments are noteworthy:

• Prospective Multicenter Trials[: There is a recognized need for further large-scale, prospective multicenter trials to more definitively delineate the role of 18F-PSMA-1007 across various clinical scenarios, refine optimal imaging protocols, and directly compare its performance against other established and emerging PSMA tracers and imaging modalities.][1] Such trials are crucial for establishing robust evidence-based guidelines.
• Managing Unspecific Bone Uptake[: A significant focus of current research is on better understanding the mechanisms behind UBU with 18F-PSMA-1007 and developing strategies to improve its differentiation from true bone metastases. This includes exploring advanced image analysis techniques (e.g., radiomics, artificial intelligence), dual-time-point imaging, the utility of quantitative parameters (SUV thresholds), and correlation with other imaging modalities like MRI.][8]
• Therapy Response Assessment and Theranostics[: While primarily a diagnostic agent, the role of 18F-PSMA-1007 in assessing response to various prostate cancer therapies, including PSMA-targeted radioligand therapy (RLT), is an area of interest.][11] Accurate assessment of PSMA expression using 18F-PSMA-1007 PET can be crucial for selecting patients who are most likely to benefit from PSMA-targeted RLT and for monitoring their response to such treatments.
• Quantitative Imaging[: The development and validation of quantitative imaging biomarkers derived from 18F-PSMA-1007 PET scans (e.g., total PSMA tumor volume, changes in SUVmax) may enhance its prognostic capabilities and its ability to predict treatment outcomes more accurately, moving beyond qualitative visual assessment.][38]
• Expansion of Indications: While currently focused on prostate cancer, the expression of PSMA in the neovasculature of other tumors could lead to investigations into the utility of 18F-PSMA-1007 for imaging other malignancies, although this is a more exploratory area.
• Logistical Optimization[: Continued improvements in production, distribution logistics (leveraging the 18F label), and cost-effectiveness will be important for ensuring broader access to 18F-PSMA-1007 imaging globally.][8]

The logistical advantages conferred by the 18F radionuclide (longer half-life, cyclotron production) position 18F-labeled PSMA ligands like PSMA-1007 favorably for potentially wider adoption compared to 68Ga-based agents, provided their diagnostic performance is robust and limitations such as UBU can be effectively managed through improved interpretation strategies or technological advancements. Continued research and clinical experience will further refine the optimal applications of 18F-PSMA-1007 in the evolving landscape of prostate cancer care.

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