⁶⁸Ga-FAP-2286 PET of Solid Tumors: Biodistribution, Dosimetry, and Comparison with ¹⁸F-FDG

Fibroblast activation protein (FAP), expressed in the tumor microenvironment of a variety of cancers, has become a target of novel PET tracers. The purpose of this report is to evaluate the imaging characteristics of ⁶⁸Ga-FAP-2286, present the first-to our knowledge-dosimetry analysis to date, and compare the agent with ¹⁸F-FDG and FAPI compounds. Methods: Patients were administered 219 ± 43 MBq of ⁶⁸Ga-FAP-2286 and scanned after 60 min. Uptake was measured in up to 5 lesions per patient and within the kidneys, spleen, liver, and mediastinum (blood pool). Absorbed doses were evaluated using MIM Encore and OLINDA/EXM version 1.1 using the International Commission on Radiological Protection publication 103 tissue weighting factor. Results: Forty-six patients were imaged with ⁶⁸Ga-FAP-2286 PET. The highest average uptake was seen in sarcoma, cholangiocarcinoma, and colon cancer. The lowest uptake was found in lung cancer and testicular cancer. The average SUV_max was significantly higher on ⁶⁸Ga-FAP-2286 PET than on ¹⁸F-FDG PET in cholangiocarcinoma (18.2 ± 6.4 vs. 9.1 ± 5.0, P = 0.007), breast cancer (11.1 ± 6.8 vs. 4.1 ± 2.2, P < 0.001), colon cancer (13.8 ± 2.2 vs. 7.6 ± 1.7, P = 0.001), hepatocellular carcinoma (9.3 ± 3.5 vs. 4.7 ± 1.3, P = 0.01), head and neck cancer (11.3 ± 3.5 vs. 7.6 ± 5.5, P = 0.04), and pancreatic adenocarcinoma (7.4 ± 1.8 vs. 3.7 ± 1.0, P = 0.01). The total-body effective dose was estimated at 1.16E-02 mSv/MBq, with the greatest absorbed organ dose in the urinary bladder wall (9.98E-02 mGy/MBq). Conclusion: ⁶⁸Ga-FAP-2286 biodistribution, dosimetry, and tumor uptake were similar to those of previously reported FAPI compounds. Additionally,⁶⁸Ga-FAP-2286 PET had consistently higher uptake than ¹⁸F-FDG PET. These results are especially promising in the setting of small-volume disease and differentiating tumor from inflammatory uptake.