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

Background: Fibroblast-activation protein (FAP) is an enzyme that appears in high numbers in cancer-associated fibroblasts of certain cancer types. \[18F\]FAPI-74 is a new PET (positron emission tomography) tracer, a substance that is injected into a person s body before an imaging scan. Researchers believe that \[18F\]FAPI-74 PET imaging may be able to visualize cancer more effectively than the approved tracers. If so, the new tracer would make it easier to find FAP-positive tumors in the body. Objective: To see if \[18F\]FAPI-74 PET scan is as good or better than other imaging methods for detecting certain cancers. Eligibility: People aged 18 years or older with one of these cancer types: 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 cancer. Design: Participants will have 2 baseline scans: an \[18F\]FAPI-74, and the approved tracer \[18F\]-FDG. The \[18F\]FAPI-74 will be infused through a needle inserted into a vein. About 1 hour later, the participant will undergo imaging. Within 1 week, participants will undergo the same scanning procedures with the approved tracer. If the baseline scan with \[18F\]FAPI-74 shows the tumor(s), scans with this tracer will be repeated when their regular treatment regimen calls for scans again. If the scan with the regular FDG also show tumors, this scan will be repeated within the same week as the repeated \[18F\]FAPI-74 scan. If \[18F\]-FAPi PET scan shows no tumor(s), scans will not be repeated. If the participant's cancer progresses within 2 years, scans may be repeated. Follow-up calls will continue for 2 years.

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.