Feasibility, Biodistribution, and Preliminary Dosimetry in Peptide-Targeted Radionuclide Therapy of Diverse Adenocarcinomas Using 177Lu-FAP-2286: First-in-Humans Results

Abstract

Fibroblast activation protein (FAP) is a promising target for diagnosis and therapy of numerous malignant tumors. FAP-2286 is the conjugate of a FAP-binding peptide, which can be labeled with radionuclides for theranostic applications. We present the first-in-humans results using 177Lu-FAP-2286 for peptide-targeted radionuclide therapy (PTRT). Methods: PTRT using 177Lu-FAP-2286 was performed on 11 patients with advanced adenocarcinomas of the pancreas, breast, rectum, or ovary after prior confirmation of uptake on 68Ga-FAP-2286 or 68Ga- FAPI-04 PET/CT. Results: Administration of 177Lu-FAP-2286 (5.8 6 2.0 GBq; range, 2.4-9.9 GBq) was well tolerated, with no adverse symptoms or clinically detectable pharmacologic effects being noticed or reported in any of the patients. The whole-body effective dose was 0.07 6 0.02 Gy/GBq (range, 0.04-0.1 Gy/GBq). The mean absorbed doses for kidneys and red marrow were 1.0 6 0.6 Gy/GBq (range, 0.4-2.0 Gy/GBq) and 0.05 6 0.02 Gy/GBq (range, 0.03-0.09 Gy/GBq), respectively. Significant uptake and long tumor retention of 177Lu-FAP- 2286 resulted in high absorbed tumor doses, such as 3.0 6 2.7 Gy/ GBq (range, 0.5-10.6 Gy/GBq) in bone metastases. No grade 4 adverse events were observed. Grade 3 events occurred in 3 patients-1 with pancytopenia, 1 with leukocytopenia, and 1 with pain flare-up; 3 patients reported a pain response. Conclusion: 177Lu-FAP- 2286 PTRT, applied in a broad spectrum of cancers, was relatively well tolerated, with acceptable side effects, and demonstrated long retention of the radiopeptide. Prospective clinical studies are warranted.