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.