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Clinical Trial
. 2024 Dec;52(1):237-246.
doi: 10.1007/s00259-024-06795-7. Epub 2024 Jul 27.

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

Seyedeh Somayyeh Banihashemian  1 , Mohammad Esmaeil Akbari  2 , Elahe Pirayesh  3 , Ghasemali Divband  4 , Abdolghafar Abolhosseini Shahrnoy  5 , Reza Nami  5 , Seyed Mohammad Mazidi  5 , Meysam Nasiri  6
Affiliations
Clinical Trial

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

Seyedeh Somayyeh Banihashemian et al. Eur J Nucl Med Mol Imaging. 2024 Dec.

Abstract

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 [177Lu]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 [177Lu]Lu-FAPI-2286. Prior to the treatment, confirmation of tumor uptake was obtained through [68Ga]Ga-FAPI-2286 PET/CT.

Results: After four cycles of PTRT with [177Lu]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 SUVmax 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: [177Lu]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.

Keywords: 177 lutetium; FAP-2286; Fibroblast activation protein (FAP); Radionuclide therapy; Sarcoma.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This prospective study was approved by the Research Ethics Committee of Shahid Beheshti University of Medical Sciences in Tehran, Iran (IR.SBMU.CRC.REC.1402.040) and a written informed consent was obtained from all patients. Consent for publication: All patients participating in the present study and the authors consent to publish and print the information contained in this article. Competing interests: The authors declare that they have no competing interests.

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