Feasibility and therapeutic potential of [177Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma

• Published in: European journal of nuclear medicine and molecular imaging 2024-12, Vol.52 (1), p.237-246
• Main Authors: Banihashemian, Seyedeh Somayyeh, Akbari, Mohammad Esmaeil, Pirayesh, Elahe, Divband, Ghasemali, Abolhosseini Shahrnoy, Abdolghafar, Nami, Reza, Mazidi, Seyed Mohammad, Nasiri, Meysam
• Format: Article
• Language: English
• Subjects: Adult; Aged; Cancer; Cardiology; Cell activation; Clinical trials; Feasibility Studies; Female; Fibroblast activation protein; Health services; Humans; Imaging; Lutetium - therapeutic use; Lutetium isotopes; Male; Medicine; Medicine & Public Health; Metastases; Metastasis; Middle Aged; Neoplasm Metastasis; Nuclear Medicine; Oncology; Original Article; Orthopedics; Patients; Positron Emission Tomography Computed Tomography; Radiation therapy; Radioisotopes; Radioisotopes - adverse effects; Radioisotopes - therapeutic use; Radiology; Radiopharmaceuticals - therapeutic use; Sarcoma; Sarcoma - diagnostic imaging; Sarcoma - radiotherapy; Side effects; Tissue Distribution; Treatment Outcome; Tumor cells; Tumors
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-024-06795-7

Introduction The unique expression pattern of fibroblast activation protein (FAP) in stromal and tumor cells, particularly in sarcomas, and its absence in normal tissues, have positioned it as a promising theragnostic approach for the detection and treatment of various cancer types. The objective of this prospective study is to assess the feasibility, safety, biodistribution, and therapeutic efficacy of [ 177 Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma. Patients and Methods Eight patients with advanced metastatic sarcoma, who were unresectable or had experienced disease recurrence following conventional treatments, underwent PTRT (peptide-targeted radionuclide therapy) using [ 177 Lu]Lu-FAPI-2286. Prior to the treatment, confirmation of tumor uptake was obtained through [ 68 Ga]Ga-FAPI-2286 PET/CT. Results After four cycles of PTRT with [ 177 Lu]Lu-FAPI-2286 (6660–7400 MBq), with a 6-8-week interval between each cycle, no grade 3 or 4 side effects were observed in the patients, and the treatment was well tolerated by all participants. The results demonstrated a 52.37% reduction in the average volume of the primary tumor, accompanied by a significant decrease in SUV max and TBR of the metastatic lesions (29.67% and 43.66% respectively), especially in cases of lung metastasis. Furthermore, besides the improvement in physical capacity, there was a noticeable reduction in pain, an increase in overall survival, and enhanced satisfaction with the treatment reported by the patients. Conclusion [ 177 Lu]Lu-FAPI-2286 PTRT, utilized for diverse cancer types, exhibited favorable tolerability in sarcoma patients, with minimal side effects, long-lasting retention of the radiopeptide within the tumor, and promising therapeutic effects. Preliminary findings of this prospective study need to be confirmed through further clinical trials.