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

Ziel/Aim Fibroblast Activation Protein FAP-2286 is the first compound with high tumor uptake, long tumor retention as well as low background activity as shown in preclinical studies. We used Lu-177 FAP-2286 PTRT first time in humans, evaluated the biodistribution and kinetics and obtained first dosimetry data.

Methodik/Methods 10 advanced adenocarcinoma patients (breast 4, pancreas 4, rectum 1, ovary 1) with lymph node (6), pulmonary (3), pleural (1), peritoneal (3), hepatic (7) and osseous (5) metastases received PTRT using 2.5 – 6.4 GBq Lu-177 FAP-2286 after confirmation of tumor uptake on prior Ga-68 FAP-2286 PET/CT (theranostics principle). Laboratory parameters (blood counts, liver and kidney function, creatine kinase, and tumor markers) were monitored. Biodistribution was analysed by post-therapy planar and SPECT/CT images. Preliminary dosimetry estimations were performed in 6 patients. Symptoms were monitored before, during, and after treatment.

Ergebnisse/Results Therapy was very well tolerated. There was self-limiting headache in 3 patients, no severe short-term side effects occurred. No significant laboratory changes were noted to date. Pain decreased (requiring less morphine) in 3 patients, e.g. in a breast carcinoma patient with disseminated bone metastases (who also had mild alopecia 10 days post-therapy). There was very low uptake in normal tissues and organs. The resulting whole body mean absorbed dose ranged from 0.05 – 0.1 Gy/GBq, that to the red marrow from 0.04 - 0.09 Gy/GBq and kidneys from 0.6 – 0.9 Gy/GBq, comparable to PRRT with Lu-177 DOTATOC. All patients demonstrated high specific tumor uptake with long retention on delayed imaging (up to 10 days).

Schlussfolgerungen/Conclusions Our first data demonstrate the feasibility of FAP-targeted theranostics. PTRT using Lu-177 FAP-2286 is - due to long tumor retention - a highly promising treatment option in a broad spectrum of cancers. Further follow-up of patients as well as prospective clinical studies are warranted.