Radiation Dosimetry and Biodistribution of ⁶⁸Ga-FAPI-46 PET Imaging in Cancer Patients

Abstract

Targeting cancer-associated fibroblasts (CAFs) has become an attractive goal for diagnostic imaging and therapy because they can constitute as much as 90% of a tumor mass. The serine protease fibroblast activation protein (FAP) is overexpressed selectively in CAFs, drawing interest in FAP as a stromal target. The quinolinebased FAP inhibitor (FAPI) PET tracer 68 Ga-FAPI-04 has been previously shown to yield high tumor-to-background ratios (TBRs) in patients with various cancers. Recent developments toward an improved compound for therapeutic application have identified FAPI-46 as a promising agent because of an increased tumor retention time in comparison with FAPI-04. Here, we present a PET biodistribution and radiation dosimetry study of 68 Ga-FAPI-46 in cancer patients. Methods: Six patients with different cancers underwent serial 68 Ga-FAPI-46 PET/CT scans at 3 time points after radiotracer injection: 10 min, 1 h, and 3 h. The source organs consisted of the kidneys, bladder, liver, heart, spleen, bone marrow, uterus, and remainder of body. OLINDA/EXM software, version 1.1, was used to fit and integrate the kinetic organ activity data to yield total-body and organ time-integrated activity coefficients and residence times and, finally, organ-absorbed doses. SUVs and TBR were generated from the contoured tumor and source-organ volumes. Spheric volumes in muscle and blood pool were also obtained for TBR (tumor SUV max /organ SUV mean ). Results: At all time points, average SUV max was highest in the liver. Tumor and organ SUV mean decreased over time, whereas TBRs in all organs but the uterus increased. The organs with the highest effective doses were bladder wall (2.41E−03 mSv/MBq), followed by ovaries (1.15E−03 mSv/MBq) and red marrow (8.49E−04 mSv/MBq). The average effective total-body dose was 7.80E−03 mSv/MBq. Conclusion: 68 Ga-FAPI-46 PET/CT has a favorable dosimetry profile, with an estimated whole-body dose of 5.3 mSv for an administration of 200 MBq (5.4 mCi) of 68 Ga-FAPI-46 (1.56 ± 0.26 mSv from the PET tracer and 3.7 mSv from 1 low-dose CT scan). The biodistribution study showed high TBRs increasing over time, suggesting high diagnostic performance and favorable tracer kinetics for potential therapeutic applications.

Clinical Results of Fibroblast Activation Protein (FAP) Specific PET and Implications for Radiotherapy Planning: Systematic Review

“…Data on FAP-specific PET is still limited. While several publications contain at least one patient with breast cancer, no dedicated analysis for target volume delineation has been performed [12,26,32,36,37]. The biggest collective consisted of four patients (3 invasive ductal carcinomas, 1 invasive lobular carcinoma) analyzed by Chen et al who found that FAP-specific PET was able to detect more lymph node metastases than FDG PET in this small sample [25].…”

68Ga-FAPI and 18F-FDG PET/CT Images in a Patient With Extrapulmonary Tuberculosis Mimicking Malignant Tumor

“… 1 – 3 FAP is an overexpression in more than 90% of epithelial carcinomas and some mesenchymal tumors, and recent studies showed that 68 Ga-FAPI might be a broad-spectrum tumor PET agent. 4 – 6 However, high uptake of 68 Ga-FAPI was also found in nontumorous lesions, including wound healing, inflammation, fibrosis, and so on. 7 , 8 This case again highlighted that 68 Ga-FAPI could gather in nontumorous lesions.…”

FAP: The Next Billion Dollar Nuclear Theranostics Target?

“…Further modifications to the FAPI compounds were performed to improve tumor retention while retaining the imaging contrast obtained with FAPI-02 and FAPI-04 (6,17,31). A further increase of tumor retention time was achieved with FAPI-46 (17,31).…”

“…A further increase of tumor retention time was achieved with FAPI-46 (17,31). 68 Ga-FAPI-46 PET/CT imaging had a favorable dosimetry profile and showed high tumor-to-background ratios increasing over time, suggesting more favorable kinetics for potential therapeutic applications (31).…”