PT  - JOURNAL ARTICLE
AU  - Richard P. Baum
AU  - Christiane Schuchardt
AU  - Aviral Singh
AU  - Maythinee Chantadisai
AU  - Franz C. Robiller
AU  - Jingjing Zhang
AU  - Dirk Mueller
AU  - Alexander Eismant
AU  - Frankis Almaguel
AU  - Dirk Zboralski
AU  - Frank Osterkamp
AU  - Aileen Hoehne
AU  - Ulrich Reineke
AU  - Christiane Smerling
AU  - Harshad R. Kulkarni
TI  - Feasibility, Biodistribution, and Preliminary Dosimetry in Peptide-Targeted Radionuclide Therapy of Diverse Adenocarcinomas Using <sup>177</sup>Lu-FAP-2286: First-in-Humans Results
AID  - 10.2967/jnumed.120.259192
DP  - 2022 Mar 01
TA  - Journal of Nuclear Medicine
PG  - 415--423
VI  - 63
IP  - 3
4099  - http://jnm.snmjournals.org/content/63/3/415.short
4100  - http://jnm.snmjournals.org/content/63/3/415.full
SO  - J Nucl Med2022 Mar 01; 63
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.