18F-Fibroblast Activation Protein Inhibitor ([18F]FAPI-74) PET Imaging for Cancer Detection

Background:

• Fibroblast-activation protein (FAP) is a transmembrane type 2 serine protease with dipeptidyl peptidase and endopeptidase activity that is overexpressed on the surface of cancer-associated fibroblasts (CAFs), a major constituent of the tumor stroma, which correlates with a poor prognosis.
• FAP-positive CAFs are present in the stromal tissue of more than 90% of epithelial carcinomas, including pancreatic, colorectal, ovarian, lung, and breast cancer among others.
• FAP has emerged in recent years as a promising target for molecular imaging with PET/Computed Tomography (CT), using radiolabeled FAP inhibitors (FAPI). FAPI labeled with 68Ga or 18F has shown great promise in cancer detection demonstrating high tumor-to-background ratios in patients across a wide array of cancers.
• While there is much clinical data with 68Ga-FAPI, there is much less data on the efficacy of [18F]FAPI-74, which is a more practical version of this PET agent due to its longer half-life.

Objective:

-To compare [18F]FAPI-74 PET imaging to 18F-fluorodeoxyglucose (18F-FDG) PET imaging and other imaging considered standard of care (SOC) (e.g., CT, and/or magnetic resonance imaging [MRI]) to detect sites of cancer in several malignancies.

Eligibility:

• >= 18 years old.
• Histologically confirmed pancreatic ductal adenocarcinoma (PDAC), cholangiocarcinoma, hepatocellular carcinoma (HCC), gastric cancer, bladder cancer, ovarian cancer, or pheochromocytoma/paraganglioma (PPGL), small cell lung or extrapulmonary neuroendocrine cancer, mesothelioma or sarcoma.
• Eastern Cooperative Oncology Group (ECOG) Performance score <= 2.

Design:

• This is a single-site imaging study enrolling participants with PDAC, cholangiocarcinoma, HCC, gastric cancer, bladder cancer, ovarian cancer, pheochromocytoma/paraganglioma, small cell lung or extrapulmonary neuroendocrine cancers, mesothelioma or sarcoma.
• All participants will undergo baseline [18F]FAPI-74 PET and 18F-FDG PET imaging.
• Participants with a positive baseline [18F]FAPI-74 PET scan (i.e., with the presence of FAPIpositive tumor/s) will undergo the second [18F]FAPI-74 PET imaging at the time of the next re-staging. Participants with a negative baseline [18F]FAPI-74 PET scan will not have post-treatment [18F]FAPI-74 PET or 18F-FDG PET scans performed on this protocol but will remain in follow-up.
• Participants with a negative baseline 18F-FDG PET scan will not be re-scanned with 18F-FDG PET but may be re-scanned with [18F]FAPI-74 PET if baseline [18F]FAPI-74 PET imaging is positive.
• All participants will be followed for 2 years following the first [18F]FAPI-74 PET scan to assess progression-free survival and 2-year overall survival. During this period, participants may undergo the additional [18F]FAPI-74 and 18F-FDG PET imaging in case of suspicion for recurrence/disease progression. These scans may be done even if the baseline [18F]FAPI-74 and/or 18F-FDG PET imaging are negative.

• INCLUSION CRITERIA:
• Histologically confirmed pancreatic ductal adenocarcinoma (PDAC), cholangiocarcinoma, hepatocellular carcinoma (HCC), gastric cancer, bladder cancer, ovarian cancer, pheochromocytoma/paraganglioma (PPGL), small cell lung cancer (SCLC) or extrapulmonary neuroendocrine cancer (EP-NEC), mesothelioma or sarcoma.
• Participants must be scheduled or intended to receive treatment for their cancer.
• Evaluable disease
• >= 18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance score <= 2.
• Individuals of child-bearing potential (IOCBP) and individuals that can father children must agree to use effective contraception (barrier, hormonal, intrauterine device (IUD), surgical sterilization, abstinence) at the study entry and for 2 months after each (18F) FAPI-74 imaging. Sperm may not be frozen or donated within the same period.
• Must be willing to discontinue breastfeeding for 2 months after each study imaging.
• The ability of participant to understand and the willingness to sign a written informed consent document.

Exclusion criteria

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to [18F]FAPI-74 or other agents used in the study.
• History of severe claustrophobia unresponsive to oral anxiolytics or history of any other condition preventing the ability to lie on the imaging scanner for up to 45 minutes.
• Weight > 350 lbs., or inability to fit within the imaging gantry.
• Positive Beta-human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test performed in IOCBP at screening.
• Uncontrolled intercurrent illness, or medical condition(s) including but not limited to renal failure, liver failure, or psychiatric illness/social situations evaluated by medical history and physical exam that would limit compliance with study requirements and potentially increase risk for the participant.
• Serum creatinine > 2 times the upper limit of normal.
• Liver transaminases (ALT, AST) greater than 3 times the upper limit of normal.