Fibroblast Activation Protein PET/CT or PET/MR Production in the Diagnosis, Staging, and Efficacy Assessment of Malignant Tumors Application
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 22
- Locations
- 1
- Primary Endpoint
- 68Ga-Fibroblast Activation Protein Inhibitor-04 Uptake in Gastrointestinal Cancer: Comparison with 18F-FDG
Study Overview
Brief Summary
This clinical trial aims to investigate the value of fibroblast activation protein PET/CT(PET/MR) in the diagnosis, staging, and evaluation of treatment outcomes in malignant tumors. The main question it aims to answer is:
Fibroblast Activation Protein PET/CT(PET/MR) whether or in which cases this assay is superior to conventional FDG examination in the diagnosis, staging, and assessment of therapeutic efficacy of malignant tumors, thinking about the reasons behind this.
Investigators will screen suitable participants among patients undergoing routine FDG examination.
- Participants will sign an informed consent form
- Undergo 68Ga-FAPI PET/CT (PET/MR) before surgery or biopsy
- Surgical resection or puncture biopsy to obtain pathologic results. Diagnosis of patients with malignant tumors at first diagnosis; clinical staging of tumors; and clinical outcomes of patients with confirmed diagnoses will be assessed after postoperative investigator follow-up.
The researchers will compare the FDG exams the participants have had to determine the effectiveness of the fibroblast activating protein test.
Detailed Description
- Title of research program Fibroblast activation protein(AFP) Positron Emission Tomography(PET)-CT or -MR production in the diagnosis of malignant tumors, staging and therapeutic evaluation of clinical applications.
Application. 2. Background Currently, 18F-FDG PET is one of the most commonly used methods for diagnosis, staging, efficacy assessment, and prognosis evaluation of malignant tumors. The basic principle of 18F-FDG PET is the Warburg effect. However, 18F-FDG has its limitations, such as low specificity, low detection rate of small tumors, mucin-secreting epithelial malignant tumors, squamous cell carcinomas, highly differentiated neuroendocrine tumors, squamous cell carcinomas, highly differentiated neuroendocrine tumors, and highly differentiated endocrine gland malignancies, among others, have low uptake.
18F-FDG is a non-specific metabolic PET tracer that can reflect glucose metabolism in malignant tumors. However, 18F-FDG can also be taken up by inflammatory lesions, infectious lesions, benign tumors, etc. Therefore, 18F-FDG tumor imaging has relative limitations. Nowadays, molecular imaging is changing from non-specific to specific radiotracer imaging. Therefore, tumor-associated fibroblasts (CAFs) have gradually become a new research hotspot.
Fibroblasts are the main host cells in the tumor microenvironment and are also the main stromal cells of solid tumors, they can interact with tumor cells, make their own morphology and physiological function changes, express a variety of cytokines, proteases, adhesion, molecular, different degree increase of tumor cell malignant characterization, and the occurrence of tumor, growth, blood vessel formation, invasion is closely related to metastasis. It has been confirmed that FAP is expressed in melanoma, colorectal cancer, breast cancer, pancreatic cancer, gastric cancer, lung cancer, esophageal cancer, ovarian cancer, cervical cancer, endometrial cancer, oral squamous cell carcinoma, and osteosarcoma, etc., and is associated with tumor growth and invasion. FAPαis a type II transmembrane glycoprotein, consisting of a primary chain of 760 amino acids with a small intracellular component or short cytoplasmic tail (6 amino acids), a transmembrane component (19 amino acids) and a large extracellular component. The monomeric form of FAPα is inactive but is activated by polymerization activity through polymerization-activation to form either the homodimer FAPα/FAPα or the heterodimer FAPα/FAPβ. This membrane-bound protein is one of the key components of the extracellular matrix and plays an important role in regulating or remodeling the tumor microenvironment. Fibroblast activation protein inhibitor Preparation (FAPI) is a novel class of probes, and the enzymatic activity of FAP provides a new diagnostic and therapeutic target. Therefore, the selection of FAPI to target FAP overexpression induced by tumor-associated fibroblasts has become a new research hotspot. Currently, new molecules such as FAPI-02, FAPI-04, FAPI-46, and other inhibitory ligands have been designed, synthesized, and conducted in vitro and in vivo experiments. Because the biological half-life of these probes matches the physical half-life of gallium-68 (Ga-68), if these molecules form new molecules after being labeled with Ga-68, the new molecules become very promising molecular probes for research. PET/CT has been gradually applied to the examination of malignant tumors, and can be used for the diagnosis of tumors, clinical staging, and evaluation of therapeutic efficacy. PET/MRI is an emerging molecular imaging method in recent years. With the popularization of integrated PET/MR imaging, combining the higher resolution and morphology of MR imaging with the N-staging and M-staging of PET has greatly improved the detection rate of some tumors and the degree of tissue invasion around the lesion. In this study, investigators propose to use fibroblast activation protein PET/CT and PET/MR for the diagnosis, staging, and evaluation of treatment effects of malignant tumors, to evaluate its real value and to make up for the insufficiency of 18F-FDG PET/CT.
- Research objectives To study the value of FAPI PET/CT and PET/MR in diagnosing, staging, and evaluating treatment effects of malignant tumors.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •18 years ≤ 75 years of age;
- •Patients with clinical suspicion of malignancy;
- •No invasive tests or treatments recently;
- •Blood routine: leukocyte > 4×109/L, neutrophil > 2×10 9/L, hemoglobin > 90g/L, platelets > 100×10 9/L;
- •Cardiac function: left ventricular ejection fraction >50%;
- •Pulmonary function tests: FEV1 ≥1.2L, FEV1% ≥50% and DLCO ≥50%;
- •Liver function: total bilirubin <1.5 times upper limit of normal (ULN); AST and ALT <1.5 times ULN;
- •Renal function: serum creatinine ≤ 1.5 times ULN, or glomerular filtration rate > 60 ml/min;
- •Participants agreed to participate in this clinical trial and signed an informed consent form;
- •Good compliance and commitment to follow the study procedures and to cooperate in the implementation of the full study;
- •No birth plans for six months.
Exclusion Criteria
- •Those with severe psychiatric symptoms, or those who are too confused to cooperate with the examination;
- •Pregnant and potentially pregnant women, lactating women;
- •Those with poor compliance.
Arms & Interventions
68Ga-FAPI PET/MRI scan
The 68Ge/68Ga generator was eluted with 0.1 M HCL solution to achieve 3.0 ml of liquid, which was mixed thoroughly with 20 µg FAPI precursor and 375 µl of 1.25 M sodium acetate. The mixture was placed in a thermostat at 95°C for 10 min. The finished liquid was passed through an activated Sep-pak 18C column and 0.8 ml of 80% ethanol was passed through the Sep-pak 18C column and a 0.2 µm microporous membrane (Pall Co., Ltd.) before the product was collected in a sterile product vial.
The equipment scan pf PET/MRI is the SIGNA PET/MR manufactured by GE Healthcare. The scan is performed approximately 40 min after injection of 1.85-3.7 MBq 68Ga-FAPI-04 per kg body weight. Breath-gated corrected step-and-shoot (SS) acquisition mode was used. The scan time was 60 ± 10 min (50-70 min). Dedicated T1- and T2-weighted images and diffusion-weighted images (DWI) of the head and neck, chest, abdomen, and pelvis were acquired.
Intervention: 68Ga-Fibroblast activation protein inhibitor (Drug)
Outcomes
Primary Outcomes
68Ga-Fibroblast Activation Protein Inhibitor-04 Uptake in Gastrointestinal Cancer: Comparison with 18F-FDG
Time Frame: up to 38 months
18F-FDG PET/CT and 68Ga-FAPI-04 PET/MR scans were acquired independently for all the participants with pathologically confirmed GI tumors and signs. The χ2 test was used to analyze these two technologies to quantitatively compare the diagnostic effects. The normalized SUVmax values (calculated by dividing a lesion's original SUVmax by the SUVmean of the descending aorta) of selected lesions were measured and analyzed by Student's t-test. A visual assessment system of the regions was prepared.
Secondary Outcomes
- Utility of 68Ga-FAPI-04 PET/MRI combines 18F-FDG PET/CT in the postoperative evaluation of gastrointestinal cancers(up to 60 months)