RT Journal Article SR Electronic T1 Feasibility, Biodistribution, and Preliminary Dosimetry in Peptide-Targeted Radionuclide Therapy of Diverse Adenocarcinomas Using 177Lu-FAP-2286: First-in-Humans Results JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 415 OP 423 DO 10.2967/jnumed.120.259192 VO 63 IS 3 A1 Richard P. Baum A1 Christiane Schuchardt A1 Aviral Singh A1 Maythinee Chantadisai A1 Franz C. Robiller A1 Jingjing Zhang A1 Dirk Mueller A1 Alexander Eismant A1 Frankis Almaguel A1 Dirk Zboralski A1 Frank Osterkamp A1 Aileen Hoehne A1 Ulrich Reineke A1 Christiane Smerling A1 Harshad R. Kulkarni YR 2022 UL http://jnm.snmjournals.org/content/63/3/415.abstract AB 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 ± 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 ± 0.02 Gy/GBq (range, 0.04–0.1 Gy/GBq). The mean absorbed doses for kidneys and red marrow were 1.0 ± 0.6 Gy/GBq (range, 0.4–2.0 Gy/GBq) and 0.05 ± 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 ± 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.