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.