Feasibility, Biodistribution and Preliminary Dosimetry in Peptide-Targeted Radionuclide Therapy (PTRT) of Diverse Adenocarcinomas using 177Lu-FAP-2286: First-in-Human Results.

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-human results using 177Lu-FAP-2286 for peptide-targeted radionuclide therapy (PTRT). Methods: PTRT using 177Lu-FAP-2286 was performed in 11 patients with advanced adenocarcinomas of pancreas, breast, rectum and ovary after prior confirmation of uptake on 68Ga-FAP-2286/-FAPI-04- PET/CT. Results: Administration of 177Lu-FAP-2286 (5.8 ± 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 doses were 0.07 ± 0.02 Gy/GBq (range 0.04 - 0.1). The mean absorbed doses for kidneys and red marrow were 1.0 ± 0.6 Gy/GBq (range 0.4 - 2.0) and 0.05 ± 0.02 Gy/GBq (range 0.03 - 0.09), respectively. Significant uptake and long tumor retention of 177Lu-FAP-2286 resulted in high absorbed tumor doses, e.g., 3.0 ± 2.7 Gy/GBq (range 0.5 - 10.6) in bone metastases. No grade (G) 4 adverse events were observed. G3 events occurred in 3 patients - 1 pancytopenia, 1 leukocytopenia and 1 pain flare-up; 3 patients reported 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.