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

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

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.

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Data availability

All data generated or analyzed during this study are included in this published article.

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Acknowledgements

The authors thank Mr. Mohammadreza Davarpanah, CEO of Pars Isotope Company, for producing the [177Lu]Lu-FAPI-2286 used in this research and all the patients who kindly participated in this study.

Funding

Not applicable.

Author information

Authors and Affiliations

  1. Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tajrish Sq, Tehran, 19899-34148, Iran

    Seyedeh Somayyeh Banihashemian & Mohammad Esmaeil Akbari

  2. Department of Nuclear Medicine, Shohada′e Tajrish Medical Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Elahe Pirayesh

  3. Khatam PET-CT Center, Khatam Hospital, Tehran, Iran

    Ghasemali Divband

  4. Parsisotope Company, Tehran, Iran

    Abdolghafar Abolhosseini Shahrnoy, Reza Nami & Seyed Mohammad Mazidi

  5. Department of Cellular and Molecular Biology, School of Biology, Damghan University, Damghan, Iran

    Meysam Nasiri

Authors
  1. Seyedeh Somayyeh Banihashemian
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Contributions

Seyedeh Somayyeh Banihashemian contributed deeply to the design of the study, managed the project, collected the patients’ data and wrote the manuscript. Mohammad Esmail Akbari designed the study, managed the project and revised the manuscript. Elahe Pirayesh, and Ghasemali Divband have injected radiopharmaceuticals to the patients and helped in data collection. Abdolghafar Abolhosseini Shahrnoy, Reza Nami, and Seyed Mohammad Mazidi have participated in the preparation of radio drugs. Meysam Nasiri analyzed and interpreted the data and wrote the paper.

Corresponding author

Correspondence to Mohammad Esmaeil Akbari.

Ethics 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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Banihashemian, S.S., Akbari, M.E., Pirayesh, E. et al. Feasibility and therapeutic potential of [177Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma. Eur J Nucl Med Mol Imaging 52, 237–246 (2024). https://doi.org/10.1007/s00259-024-06795-7

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