The Application of [⁶⁸Ga]‐Labeled FAPI‐04 PET/CT for Targeting and Early Detection of Pancreatic Carcinoma in Patient‐Derived Orthotopic Xenograft Models

Abstract

[18F]FDG as a probe of PET/CT is a radiolabeled glucose analogue taken up by most cells, but its batch activity is limited. [68Ga]FAPI-04 is a promising alternative based on a fibroblast activation protein-specific inhibitor (FAPI) labeled with radiotracer FAP. Here, a series of databases suggested that FAP expression was significantly different in pancreatic cancer compared to normal tissue. The FAP-positive fibroblasts were evaluated around the tumor cells and the stroma. A patient-derived orthotopic xenograft (PDOX) model of pancreatic adenocarcinoma (PDAC) exhibits significantly higher quantitative uptake of [68Ga]FAPI-04 (P < 0.05) than [18F]FDG PET/CT in various organs. Because of relatively high (T/M) ratios, the [68Ga]FAPI-04 is excellent for B-mode ultrasound, NIRF, and PET/CT. Thus, [68Ga]FAPI-04 PET displayed a better tumor specificity and can be a potential application for the early detection of pancreatic cancer.

[18F] AlF‑NOTA‑FAPI‑04 PET/CT as a promising tool for imaging fibroblast activation protein in gastrointestinal system cancers: a prospective investigation of comparative analysis with 18F-FDG

“…We noted two instances where diffuse 18 F-FAPI-04 uptake occurred due to tumor-associated pancreatitis, which could potentially cause an overestimation of tumor volume. Guided by prior research [ 16 ], we executed an additional 2-hour delayed 18 F-FAPI-04 PET/CT scan to aid in differential diagnosis. The results from these dual-time scans showed differential kinetics between tumor-associated pancreatitis, which had decreased uptake, and pancreatic cancer, which demonstrated stable uptake.…”

Recent Pre-Clinical Advancements in Nuclear Medicine: Pioneering the Path to a Limitless Future

“…Subsequent studies in mouse models of PDAC showed significant growth delay after a single injection of 225 Ac-FAPI-04, further supporting its potential as a therapeutic agent [108]. FAPI-04 ( 68 Ga-FAPI) was also used to detect early lesions in an orthotopic model of PDAC, using PDXs tumors [109]. This molecule was also labeled with 131 I and 211 At for PRRT in gliomas.…”

Advances in PET/CT Imaging for Breast Cancer

“…Continued development of these promising compounds has led to multiple preclinical studies, providing data to support the further translation of these compounds. One such study evaluated the potential of 68 Ga-FAPI-04 PET imaging in patient-derived pancreatic cancer xenografts, finding that 68 FAPI-04 displayed superior tumor-to-background uptake than 18 FDG-PET [182]. Another study evaluated the theranostic combination of 64 Cu-FAPI-04 and 225 Ac-FAPI-04, demonstrating excellent tumor targeting, although in most organs 64 Cu-FAPI-04 accumulation was significantly higher than 68 Ga-FAPI-04, suggesting that the latter may be superior for FAP PET imaging.…”