<sup>177</sup>Lu-FAP-2286 in treatment of advanced digestive system tumors: a preliminary study of efficacy and safety_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

丁一 ^1,2,3 , 高本见 ^1,2,3 , 刘永发 ^1,2,3 , 杨小李 ^1,2,3 ,  陈跃 ^3,4 ,  李波 ^1,2,3

1. Department of General Surgery/Hepatopancreatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P. R. China;
2. Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P. R. China;
3. Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan 646000, P. R. China;
4. Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P. R. China;

Corresponding author：

陈跃, Email: chenyue5523@126.com; 李波, Email: liboer2002@126.com

Keywords：

digestive system tumor; ¹⁷⁷Lu-FAP-2286; radioligand therapy; efficacy; safety

DOI：

10.7507/1007-9424.202504068

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To evaluate the efficacy and safety of ¹⁷⁷Lu-FAP-2286 radioligand therapy (RLT) in advanced digestive system malignancies and explore its clinical potential as a novel targeted therapeutic approach. Methods This retrospective analysis examined clinical data from 19 patients with advanced digestive system tumors who received ¹⁷⁷Lu-FAP-2286 treatment at the Affiliated Hospital of Southwest Medical University between June 2023 and December 2024. Treatment response was assessed using response evaluation criteria in solid tumor (RECIST) 1.1 criteria and modified PERCIST（PET response criteria in solid tumor, PERCIST） 1.0 guidelines. Adverse events (AEs) were graded according to CTCAE v5.0. Results At the last follow-up, consistent therapeutic outcomes were observed between RECIST 1.1 and PERCIST 1.0 evaluations, we observed 2 cases of partial response / partial metabolic response, 4 cases of stable disease / stable metabolic disease, and 13 cases of progressive disease / progressive metabolic disease, demonstrating an objective response rate of 10.5% (2/19) and disease control rate of 31.6% (6/19). Post-treatment monitoring revealed 7 AEs of grade 2 and 1 AE of grade 1, with no occurrence of grade 3–4 haematological or hepatorenal toxicities. Common treatment-related symptoms, including nausea, decreased appetite, and fatigue, showed spontaneous resolution over time. Conclusions Preliminary findings indicate that ¹⁷⁷Lu-FAP-2286 exhibits favourable safety and tolerability in patients with advanced digestive system malignancies while demonstrating efficacy in controlling disease progression for a subset of patients. However, multicenter prospective studies with larger cohorts are warranted to further validate its long-term efficacy and identify clinical characteristics of digestive system malignancy patients who may benefit.

1.	Güthle M, Ettrich T, Seufferlein T. Immunotherapy in gastrointestinal cancers. Visc Med, 2020, 36(3): 231-237.
2.	Turkes F, Mencel J, Starling N. Targeting the immune milieu in gastrointestinal cancers. J Gastroenterol, 2020, 55(10): 909-926.
3.	Barsouk A, Thandra KC, Saginala K, et al. Chemical risk factors of primary liver cancer: an update. Hepat Med, 2021, 12: 179-188.
4.	Dolcetti R, De Re V, Canzonieri V. Immunotherapy for gastric cancer: time for a personalized approach? Int J Mol Sci, 2018, 19(6): 1602. doi: 10.3390/ijms19061602.
5.	Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med, 2021, 385(12): 1091-1103.
6.	Meyer C, Dahlbom M, Lindner T, et al. Radiation dosimetry and biodistribution of ⁶⁸Ga-FAPI-46 PET imaging in cancer patients. J Nucl Med, 2020, 61(8): 1171-1177.
7.	Fitzgerald AA, Weiner LM. The role of fibroblast activation protein in health and malignancy. Cancer Metastasis Rev, 2020, 39(3): 783-803.
8.	Zboralski D, Hoehne A, Bredenbeck A, et al. Preclinical evaluation of FAP-2286 for fibroblast activation protein targeted radionuclide imaging and therapy. Eur J Nucl Med Mol Imaging, 2022, 49(11): 3651-3667.
9.	Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1. 1). Eur J Cancer, 2009, 45(2): 228-247.
10.	O JH, Lodge MA, Wahl RL. Practical PERCIST: a simplified guide to PET response criteria in solid tumors 1. 0. Radiology, 2016, 280(2): 576-584.
11.	Kratochwil C, Flechsig P, Lindner T, et al. ⁶⁸Ga-FAPI PET/CT: tracer uptake in 28 different kinds of cancer. J Nucl Med, 2019, 60(6): 801-805.
12.	Li M, Younis MH, Zhang Y, et al. Clinical summary of fibroblast activation protein inhibitor-based radiopharmaceuticals: cancer and beyond. Eur J Nucl Med Mol Imaging, 2022, 49(8): 2844-2868.
13.	Assadi M, Rekabpour SJ, Jafari E, et al. Feasibility and therapeutic potential of ¹⁷⁷Lu-fibroblast activation protein inhibitor-46 for patients with relapsed or refractory cancers: a preliminary study. Clin Nucl Med, 2021, 46(11): e523-e530.
14.	Kuyumcu S, Kovan B, Sanli Y, et al. Safety of fibroblast activation protein-targeted radionuclide therapy by a low-dose dosimetric approach using ¹⁷⁷Lu-FAPI04. Clin Nucl Med, 2021, 46(8): 641-646.
15.	Lindner T, Loktev A, Altmann A, et al. Development of quinoline-based theranostic ligands for the targeting of fibroblast activation protein. J Nucl Med, 2018, 59(9): 1415-1422.
16.	Privé BM, Boussihmad MA, Timmermans B, et al. Fibroblast activation protein-targeted radionuclide therapy: background, opportunities, and challenges of first (pre)clinical studies. Eur J Nucl Med Mol Imaging, 2023, 50(7): 1906-1918.
17.	Liu X, Li D, Ma T, et al. Autophagy inhibition improves the targeted radionuclide therapy efficacy of ¹³¹I-FAP-2286 in pancreatic cancer xenografts. J Transl Med, 2024, 22(1): 156. doi: 10.1186/s12967-024-04958-6.
18.	Banihashemian SS, Akbari ME, 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, 2024, 52(1): 237-246.
19.	Pang Y, Zhao L, Meng T, et al. PET imaging of fibroblast activation protein in various types of cancer using ⁶⁸Ga-FAP-2286: comparison with ¹⁸F-FDG and ⁶⁸Ga-FAPI-46 in a single-center, prospective study. J Nucl Med, 2023, 64(3): 386-394.
20.	Kline B, Yadav S, Seo Y, et al. ⁶⁸Ga-FAP-2286 PET of solid tumors: biodistribution, dosimetry, and comparison with ¹⁸F-FDG. J Nucl Med, 2024, 65(6): 938-943.
21.	Moris D, Palta M, Kim C, et al. Advances in the treatment of intrahepatic cholangiocarcinoma: an overview of the current and future therapeutic landscape for clinicians. CA Cancer J Clin, 2023, 73(2): 198-222.
22.	Biller LH, Schrag D. Diagnosis and treatment of metastatic colorectal cancer: a review. JAMA, 2021, 325(7): 669-685.
23.	Stoop TF, Javed AA, Oba A, et al. Pancreatic cancer. Lancet, 2025, 405(10485): 1182-1202.
24.	Zhan T, Betge J, Schulte N, et al. Digestive cancers: mechanisms, therapeutics and management. Signal Transduct Target Ther, 2025, 10(1): 24. doi: 10.1038/s41392-024-02097-4.
25.	Teng F, Kong L, Meng X, et al. Radiotherapy combined with immune checkpoint blockade immunotherapy: achievements and challenges. Cancer Lett, 2015, 365(1): 23-29.
26.	Theelen WSME, Chen D, Verma V, et al. Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Respir Med, 2021, 9(5): 467-475.
27.	Chen J, Zhou Y, Pang Y, et al. FAP-targeted radioligand therapy with ⁶⁸Ga/¹⁷⁷Lu-DOTA-2P(FAPI)2 enhance immunogenicity and synergize with PD-L1 inhibitors for improved antitumor efficacy. J Immunother Cancer, 2025, 13(1): e010212. doi: 10.1136/jitc-2024-010212.
28.	Shi J, Gao H, Wu Y, et al. Nuclear imaging of PD-L1 expression promotes the synergistic antitumor efficacy of targeted radionuclide therapy and immune checkpoint blockade. Eur J Nucl Med Mol Imaging, 2025, 52(3): 955-969.
29.	Ferdinandus J, Costa PF, Kessler L, et al. Initial clinical experience with ⁹⁰Y-FAPI-46 radioligand therapy for advanced-stage solid tumors: a case series of 9 patients. J Nucl Med, 2022, 63(5): 727-734.
30.	Baum RP, Schuchardt C, Singh A, et al. Feasibility, biodistribution, and preliminary dosimetry in peptide-targeted radionuclide therapy of diverse adenocarcinomas using ¹⁷⁷Lu-FAP-2286: first-in-humans results. J Nucl Med, 2022, 63(3): 415-423.

1. Güthle M, Ettrich T, Seufferlein T. Immunotherapy in gastrointestinal cancers. Visc Med, 2020, 36(3): 231-237.
2. Turkes F, Mencel J, Starling N. Targeting the immune milieu in gastrointestinal cancers. J Gastroenterol, 2020, 55(10): 909-926.
3. Barsouk A, Thandra KC, Saginala K, et al. Chemical risk factors of primary liver cancer: an update. Hepat Med, 2021, 12: 179-188.
4. Dolcetti R, De Re V, Canzonieri V. Immunotherapy for gastric cancer: time for a personalized approach? Int J Mol Sci, 2018, 19(6): 1602. doi: 10.3390/ijms19061602.
5. Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med, 2021, 385(12): 1091-1103.
6. Meyer C, Dahlbom M, Lindner T, et al. Radiation dosimetry and biodistribution of ⁶⁸Ga-FAPI-46 PET imaging in cancer patients. J Nucl Med, 2020, 61(8): 1171-1177.
7. Fitzgerald AA, Weiner LM. The role of fibroblast activation protein in health and malignancy. Cancer Metastasis Rev, 2020, 39(3): 783-803.
8. Zboralski D, Hoehne A, Bredenbeck A, et al. Preclinical evaluation of FAP-2286 for fibroblast activation protein targeted radionuclide imaging and therapy. Eur J Nucl Med Mol Imaging, 2022, 49(11): 3651-3667.
9. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1. 1). Eur J Cancer, 2009, 45(2): 228-247.
10. O JH, Lodge MA, Wahl RL. Practical PERCIST: a simplified guide to PET response criteria in solid tumors 1. 0. Radiology, 2016, 280(2): 576-584.
11. Kratochwil C, Flechsig P, Lindner T, et al. ⁶⁸Ga-FAPI PET/CT: tracer uptake in 28 different kinds of cancer. J Nucl Med, 2019, 60(6): 801-805.
12. Li M, Younis MH, Zhang Y, et al. Clinical summary of fibroblast activation protein inhibitor-based radiopharmaceuticals: cancer and beyond. Eur J Nucl Med Mol Imaging, 2022, 49(8): 2844-2868.
13. Assadi M, Rekabpour SJ, Jafari E, et al. Feasibility and therapeutic potential of ¹⁷⁷Lu-fibroblast activation protein inhibitor-46 for patients with relapsed or refractory cancers: a preliminary study. Clin Nucl Med, 2021, 46(11): e523-e530.
14. Kuyumcu S, Kovan B, Sanli Y, et al. Safety of fibroblast activation protein-targeted radionuclide therapy by a low-dose dosimetric approach using ¹⁷⁷Lu-FAPI04. Clin Nucl Med, 2021, 46(8): 641-646.
15. Lindner T, Loktev A, Altmann A, et al. Development of quinoline-based theranostic ligands for the targeting of fibroblast activation protein. J Nucl Med, 2018, 59(9): 1415-1422.
16. Privé BM, Boussihmad MA, Timmermans B, et al. Fibroblast activation protein-targeted radionuclide therapy: background, opportunities, and challenges of first (pre)clinical studies. Eur J Nucl Med Mol Imaging, 2023, 50(7): 1906-1918.
17. Liu X, Li D, Ma T, et al. Autophagy inhibition improves the targeted radionuclide therapy efficacy of ¹³¹I-FAP-2286 in pancreatic cancer xenografts. J Transl Med, 2024, 22(1): 156. doi: 10.1186/s12967-024-04958-6.
18. Banihashemian SS, Akbari ME, 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, 2024, 52(1): 237-246.
19. Pang Y, Zhao L, Meng T, et al. PET imaging of fibroblast activation protein in various types of cancer using ⁶⁸Ga-FAP-2286: comparison with ¹⁸F-FDG and ⁶⁸Ga-FAPI-46 in a single-center, prospective study. J Nucl Med, 2023, 64(3): 386-394.
20. Kline B, Yadav S, Seo Y, et al. ⁶⁸Ga-FAP-2286 PET of solid tumors: biodistribution, dosimetry, and comparison with ¹⁸F-FDG. J Nucl Med, 2024, 65(6): 938-943.
21. Moris D, Palta M, Kim C, et al. Advances in the treatment of intrahepatic cholangiocarcinoma: an overview of the current and future therapeutic landscape for clinicians. CA Cancer J Clin, 2023, 73(2): 198-222.
22. Biller LH, Schrag D. Diagnosis and treatment of metastatic colorectal cancer: a review. JAMA, 2021, 325(7): 669-685.
23. Stoop TF, Javed AA, Oba A, et al. Pancreatic cancer. Lancet, 2025, 405(10485): 1182-1202.
24. Zhan T, Betge J, Schulte N, et al. Digestive cancers: mechanisms, therapeutics and management. Signal Transduct Target Ther, 2025, 10(1): 24. doi: 10.1038/s41392-024-02097-4.
25. Teng F, Kong L, Meng X, et al. Radiotherapy combined with immune checkpoint blockade immunotherapy: achievements and challenges. Cancer Lett, 2015, 365(1): 23-29.
26. Theelen WSME, Chen D, Verma V, et al. Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Respir Med, 2021, 9(5): 467-475.
27. Chen J, Zhou Y, Pang Y, et al. FAP-targeted radioligand therapy with ⁶⁸Ga/¹⁷⁷Lu-DOTA-2P(FAPI)2 enhance immunogenicity and synergize with PD-L1 inhibitors for improved antitumor efficacy. J Immunother Cancer, 2025, 13(1): e010212. doi: 10.1136/jitc-2024-010212.
28. Shi J, Gao H, Wu Y, et al. Nuclear imaging of PD-L1 expression promotes the synergistic antitumor efficacy of targeted radionuclide therapy and immune checkpoint blockade. Eur J Nucl Med Mol Imaging, 2025, 52(3): 955-969.
29. Ferdinandus J, Costa PF, Kessler L, et al. Initial clinical experience with ⁹⁰Y-FAPI-46 radioligand therapy for advanced-stage solid tumors: a case series of 9 patients. J Nucl Med, 2022, 63(5): 727-734.
30. Baum RP, Schuchardt C, Singh A, et al. Feasibility, biodistribution, and preliminary dosimetry in peptide-targeted radionuclide therapy of diverse adenocarcinomas using ¹⁷⁷Lu-FAP-2286: first-in-humans results. J Nucl Med, 2022, 63(3): 415-423.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Latest Articles¹⁷⁷Lu-FAP-2286 in treatment of advanced digestive system tumors: a preliminary study of efficacy and safety

Abstract Full text Figures/Tables Video References Cited by

Format

Content

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Latest Articles177Lu-FAP-2286 in treatment of advanced digestive system tumors: a preliminary study of efficacy and safety

Abstract Full text Figures/Tables Video References Cited by

Format

Content

Latest Articles¹⁷⁷Lu-FAP-2286 in treatment of advanced digestive system tumors: a preliminary study of efficacy and safety