FAPI-PET imaging in solid tumors
- Registration Number
- 2024-514967-25-00
- Lead Sponsor
- Karolinska University Hospital
- Brief Summary
To improve non-invasive diagnostics of malignancy in tumors of pancreas, stomach, and bile ducts, as well as in epithelial ovarian cancer (EOC)
- Detailed Description
Malignant tumors exceeding 1-2 mm in size require formation of a supporting stroma, which includes vascular cells, inflammatory cells and fibroblasts . Several organs in the upper gastro-intestinal tract are known to develop tumors with strong desmoplastic reaction characterized by pervasive growth of tumor stroma. The pancreas, stomach, bile ducts and ovaries are all organs with this property. Within tumor stroma, a subpopulation of fibroblasts called cancer-associated fibroblasts (CAFs) are known to be involved in growth, migration and progression of the tumor.
The Fibroblast Activation Protein (FAP) is one of the more prominent stroma markers and was the focus in the development of an agent for imaging and, eventually, even targeted radionuclide therapy. FAP is a type II membrane bound glycoprotein absent or only expressed at insignificant levels, in normal tissues in adults. The FAP inhibitor, FAPI, gets selectively enriched in tissues where its target protein is expressed and there is no or very limited FAPI uptake in all normal organs. This opens new possibilities for the detection of malignant lesions with higher stromal content based on the high contrast positron emission tomography (PET) images obtained with a 68-Gallium (68Ga) radiolabeled - FAPI compound. As cancers in pancreas, stomach, bile ducts and ovaries are all characterized by abundant desmoplasia that constitutes up to 90% of the total tumor volume and contains extracellular matrix, immune cells, vasculature and CAFs, it would be suitable for targeted imaging with FAPI.
Preliminary studies show elevated FAPI uptake in many tumors rich in fibroblasts along with low background uptake. The main objective of this prospective study is to improve non-invasive diagnostics of malignancy in tumors of pancreas, stomach, bile ducts and ovaries, all known for a strong desmoplastic reaction by evaluating the diagnostic accuracy of PET/CT with a novel radiotracer, FAPI in the primary diagnosis and staging of such cancers.
Recruitment & Eligibility
- Status
- Authorised, recruitment pending
- Sex
- Not specified
- Target Recruitment
- 410
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The subject has given written consent to participate in the study
-
The subject has suspected pancreatic, gastric, biliary or epithelial ovarian cancer based on multimodal strategy including markers in blood, markers in tissue and imaging diagnostics; scheduled for surgical removal of this lesion with histopathological confirmation of diagnosis.
Age ≤18 year
Pregnancy and lactation
Known metastatic disease (Not applicable for the EOC study group as most cases are already metastasized at the point of primary diagnosis)
Significantly reduced renal function
Allergy to iodinated contrast media
Subjects that for some reason are unable to exercise their own rights, such as cognitive function impairment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Non cancer patients 68Ga-FAPI-46 Non cancer patients operated for non-malignant diseases in pancreas during the same period of time will be investigated with the same procedure. Cancer patients PET/CT * Adults with suspected cancer of either pancreas, bile ducts or stomach * Adults with primary and recurrent epithelial ovarian cancer (EOC) Non cancer patients PET/CT Non cancer patients operated for non-malignant diseases in pancreas during the same period of time will be investigated with the same procedure. Cancer patients 68Ga-FAPI-46 * Adults with suspected cancer of either pancreas, bile ducts or stomach * Adults with primary and recurrent epithelial ovarian cancer (EOC)
- Primary Outcome Measures
Name Time Method Surgery with histopathological confirmation of diagnosis Surgery with histopathological confirmation of diagnosis
- Secondary Outcome Measures
Name Time Method To evaluate FAPI- PET/CT as a staging tool for all included cancer entities, the secondary endpoint variables will be assessed with the histopathological diagnosis as a refence standard for regional or distant lymph nodes and/or resected local or distant metastatic tumor tissue when present. To evaluate FAPI- PET/CT as a staging tool for all included cancer entities, the secondary endpoint variables will be assessed with the histopathological diagnosis as a refence standard for regional or distant lymph nodes and/or resected local or distant metastatic tumor tissue when present.
To investigate the correlation between in-vivo uptake of FAPI and ex-vivo immunohistochemically determined biomarker (FAP, PDGFR-α, PDGFR-β and α-SMA) expression in the stroma of these tumors, postsurgical histopathological confirmation of diagnosis will be used for confirmation of tumor histology (benign and malignant). To investigate the correlation between in-vivo uptake of FAPI and ex-vivo immunohistochemically determined biomarker (FAP, PDGFR-α, PDGFR-β and α-SMA) expression in the stroma of these tumors, postsurgical histopathological confirmation of diagnosis will be used for confirmation of tumor histology (benign and malignant).
Assessment of FAPI- PET/CT and stroma markers as prognostic factors in patients with these cancers will be performed by recording disease free survival (DFS) and overall survival OS at 1 – year, 2 – years and 5 – years clinical follow – ups continuously during the follow – up period of the study. Assessment of FAPI- PET/CT and stroma markers as prognostic factors in patients with these cancers will be performed by recording disease free survival (DFS) and overall survival OS at 1 – year, 2 – years and 5 – years clinical follow – ups continuously during the follow – up period of the study.
4. To investigate the difference in diagnostic accuracy of FAPI- PET/CT compared to conventional radiology performed according to clinical routine, either postsurgical histopathological or histopathological/cytological (in the case of tissue biopsy material) confirmation of diagnosis will be used as a reference standard for differential diagnosis between malignant and benign lesions as well as for N and M staging 4. To investigate the difference in diagnostic accuracy of FAPI- PET/CT compared to conventional radiology performed according to clinical routine, either postsurgical histopathological or histopathological/cytological (in the case of tissue biopsy material) confirmation of diagnosis will be used as a reference standard for differential diagnosis between malignant and benign lesions as well as for N and M staging
To investigate the frequency of Adverse Events (AEs), Adverse Reactions (ARs), Serious Adverse Events (SAEs) and Suspected Unexpected Serious Adverse Reactions (SUSARs) To investigate the frequency of Adverse Events (AEs), Adverse Reactions (ARs), Serious Adverse Events (SAEs) and Suspected Unexpected Serious Adverse Reactions (SUSARs)
Trial Locations
- Locations (1)
Karolinska University Hospital
🇸🇪Huddinge, Sweden
Karolinska University Hospital🇸🇪Huddinge, SwedenRimma AxelssonSite contact+46708227622rimma.axelsson@ki.se