A preliminary study on the safety and efficacy of 177Lu-FAP-2286 in gastrointestinal tumours with positive FAP expression

  • Radiother Oncol. 2025 Oct 4:213:111195. doi: 10.1016/j.radonc.2025.111195.
Xuecheng Bai  1 ,  Na Zhang  2 ,  Hong Liu  3 ,  Yang Xie  2 ,  Benjian Gao  1 ,  Tingting Xu  2 ,  Zhiqiao Liu  2 ,  Peng Wang  2 ,  Wenlu Zheng  2 ,  Xiaoli Yang  1 ,  Yue Chen  4 ,  Bo Li  5
Affiliations
  • 1. Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, No. 25 Taiping St, Jiangyang District, Luzhou 646000 Sichuan, People's Republic of China; Academician(Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping St, Jiangyang District, Luzhou 646000 Sichuan, People's Republic of China; Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, No. 25 Taiping St, Jiangyang District, Luzhou 646000 Sichuan, People's Republic of China.
  • 2. Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping St, Jiangyang District, Luzhou 646000 Sichuan, People's Republic of China; Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, No. 25 Taiping St, Jiangyang District, Luzhou 646000 Sichuan, People's Republic of China; Institute of Nuclear Medicine, Southwest Medical University, No. 25 Taiping St, Jiangyang District, Luzhou 646000 Sichuan, People's Republic of China.
  • 3. Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, No. 25 Taiping St, Jiangyang District, Luzhou 646000 Sichuan, People's Republic of China; Academician(Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping St, Jiangyang District, Luzhou 646000 Sichuan, People's Republic of China; Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, No. 25 Taiping St, Jiangyang District, Luzhou 646000 Sichuan, People's Republic of China; Department of Hepatobiliary and Pancreatic Surgery, Dazhou Central Hospital, 635000 Sichuan, People's Republic of China.
  • 4. Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping St, Jiangyang District, Luzhou 646000 Sichuan, People's Republic of China; Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, No. 25 Taiping St, Jiangyang District, Luzhou 646000 Sichuan, People's Republic of China; Institute of Nuclear Medicine, Southwest Medical University, No. 25 Taiping St, Jiangyang District, Luzhou 646000 Sichuan, People's Republic of China. Electronic address: [email protected].
  • 5. Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, No. 25 Taiping St, Jiangyang District, Luzhou 646000 Sichuan, People's Republic of China; Academician(Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping St, Jiangyang District, Luzhou 646000 Sichuan, People's Republic of China; Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, No. 25 Taiping St, Jiangyang District, Luzhou 646000 Sichuan, People's Republic of China. Electronic address: [email protected].
PMID: 41052603 DOI: 10.1016/j.radonc.2025.111195
Abstract

Background and purpose: Preclinical studies of fibroblast activation protein (FAP)-2286 showed improved tumor-targeting specificity and prolonged intratumoral retention. However, clinical trials on the safety and efficacy of 177Lu-FAP-2286 for gastrointestinal tumors are limited. This study aims to evaluate its safety and efficacy in patients with FAP-positive gastrointestinal tumors.

Materials and methods: A prospective, single-center, single-arm clinical trial was conducted at the Affiliated Hospital of Southwest Medical University from December 2020 to December 2024. After confirming FAP expression in tumor lesions using 68Ga-FAP-2286, 177Lu-FAP-2286 targeted radiotherapy was performed. Tumor response was assessed using RECIST 1.1 and PERCIST 1.0 criteria. Adverse events were graded according to the CTCAE 5.0.

Results: Fourteen participants (mean age, 62.1 ± 7.6 years) completed 30 treatment cycles. Four participants (28.6 %) achieved stable disease, and ten (71.4 %) exhibited progressive disease. The disease control rate was 28.6 %. No significant correlations were found between clinical efficacy and imaging parameters. No grade III or IV adverse events occurred, but transient nausea, vomiting, and diarrhea were observed.

Conclusions: 177Lu-FAP-2286 demonstrated good feasibility and safety in treating FAP-positive gastrointestinal tumors, resulting in disease stabilization in a subset of patients.

Keywords
(177)Lu-FAP-2286; FAP; Gastrointestinal tumours; TRT.
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