Current application of <sup>177</sup>Lu in solid tumors_West China Medical Journal

Authors：

NIU Tingting ¹ ,  DU Xiaobo ^1,2

1. Department of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan 637000, P. R. China;
2. Department of Oncology, Mianyang Central Hospital, Mianyang, Sichuan 621000, P. R. China;

Corresponding author：

DU Xiaobo, Email: duxiaobo2005@126.com

Keywords：

Lutetium-177; prostate cancer; neuroendocrine tumor; targeted radionuclide therapy

DOI：

10.7507/1002-0179.202301003

Video：

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Abstract Full text Figures/Tables Video References Cited by

Radionuclides can be labeled on biomolecules with specific binding ability. By binding with specific targets of tumors, particles such as α or β emitted by the radionuclides will specifically irradiate tumors and produce ionizing radiation effects, resulting in cell senescence and death within the irradiation range, achieving tumor treatment results, and this way has little impact on surrounding normal tissues. Lutetium-177 (¹⁷⁷Lu) can emit γ rays for CT imaging, and can also emit β rays for tumor treatment, so ¹⁷⁷Lu is now one of the radionuclides that can be used for integrated diagnosis and treatment. This review summarizes the clinical application of ¹⁷⁷Lu in several solid tumors, in conjunction with currently published research.

Citation： NIU Tingting, DU Xiaobo. Current application of ¹⁷⁷Lu in solid tumors. West China Medical Journal, 2023, 38(7): 1100-1106. doi: 10.7507/1002-0179.202301003 Copy

1.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2.	中国共产党中央委员会, 中华人民共和国国务院. “健康中国 2030”规划纲要. 中国肿瘤, 2019(10): 724.
3.	卓连刚, 杨宇川, 岳海东, 等. DGA 树脂辅助的循环淋洗技术制备无载体镥[¹⁷⁷Lu]. 同位素, 2022, 35(3): 217-223.
4.	杨宇川, 阚文涛, 杨夏, 等. ¹⁷⁷Lu 放射性治疗药物研究新进展. 同位素, 2022, 35(3): 164-178.
5.	张朋俊, 张露露, 卜婷, 等. ¹⁷⁷Lu 标记的放射性药物制备方法的比较及初步临床应用. 中华核医学与分子影像杂志, 2022, 42(10): 597-601.
6.	Zakaly HMH, Mostafa MYA, Deryabina D, et al. Comparative studies on the potential use of ¹⁷⁷Lu-based radiopharmaceuticals for the palliative therapy of bone metastases. Int J Radiat Biol, 2020, 96(6): 779-789.
7.	冯婷婷, 成伟华, 王斌, 等. ¹⁷⁷Lu 标记放射性药物临床研究进展. 标记免疫分析与临床, 2018, 25(11): 1750-1756.
8.	Heston WD. Characterization and glutamyl preferring carboxypeptidase function of prostate specific membrane antigen: a novel folate hydrolase. Urology, 1997, 49(Suppl 3A): 104-112.
9.	Boegemann M, Schrader AJ, Rahbar K. ¹⁷⁷Lu-PSMA therapy : current evidence for use in the treatment of patients with metastatic prostate cancer. Urologe A, 2017, 56(11): 1440-1444.
10.	Ghosh A, Heston WD. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem, 2004, 91(3): 528-539.
11.	Miller KD, Nogueira L, Devasia T, et al. Cancer treatment and survivorship statistics, 2022. CA Cancer J Clin, 2022, 72(5): 409-436.
12.	Zeng H, Chen W, Zheng R, et al. Changing cancer survival in China during 2003-15: a pooled analysis of 17 population-based cancer registries. Lancet Glob Health, 2018, 6(5): e555-e567.
13.	Achard V, Panje CM, Engeler D, et al. Localized and locally advanced prostate cancer: treatment options. Oncology, 2021, 99(7): 413-421.
14.	Desai K, McManus JM, Sharifi N. Hormonal therapy for prostate cancer. Endocr Rev, 2021, 42(3): 354-373.
15.	Schaeffer EM, Srinivas S, Adra N, et al. NCCN guidelines^® insights: prostate cancer, version 1.2023. J Natl Compr Canc Netw, 2022, 20(12): 1288-1298.
16.	Naseer F, Ahmad T, Kousar K, et al. Advanced therapeutic options for treatment of metastatic castration resistant prostatic adenocarcinoma. Front Pharmacol, 2021, 12: 728054.
17.	Cao J, Chen Y, Hu M, et al. ¹⁷⁷Lu-PSMA-RLT of metastatic castration-resistant prostate cancer: limitations and improvements. Ann Nucl Med, 2021, 35(8): 861-870.
18.	Sadaghiani MS, Sheikhbahaei S, Werner RA, et al. ¹⁷⁷Lu-PSMA radioligand therapy effectiveness in metastatic castration-resistant prostate cancer: an updated systematic review and meta-analysis. Prostate, 2022, 82(7): 826-835.
19.	谢彦, 李澄, 张露露, 等. ¹⁷⁷Lu-PSMA-I&T 治疗前列腺癌的疗效评价. 中华核医学与分子影像杂志, 2021, 41(6): 356-361.
20.	Weineisen M, Schottelius M, Simecek J, et al. ⁶⁸Ga- and ¹⁷⁷Lu-labeled PSMA I&T: optimization of a PSMA-targeted theranostic concept and first proof-of-concept human studies. J Nucl Med, 2015, 56(8): 1169-1176.
21.	Barna S, Haug AR, Hartenbach M, et al. Dose calculations and dose-effect relationships in ¹⁷⁷Lu-PSMA I&T radionuclide therapy for metastatic castration-resistant prostate cancer. Clin Nucl Med, 2020, 45(9): 661-667.
22.	Hartrampf PE, Weinzierl FX, Serfling SE, et al. Hematotoxicity and nephrotoxicity in prostate cancer patients undergoing radioligand therapy with [¹⁷⁷Lu] Lu-PSMA I&T. Cancers (Basel), 2022, 14(3): 647.
23.	Bu T, Zhang L, Yu F, et al. ¹⁷⁷Lu-PSMA-I&T radioligand therapy for treating metastatic castration-resistant prostate cancer: a single-centre study in East Asians. Front Oncol, 2022, 12: 835956.
24.	Karimzadeh A, Heck M, Tauber R, et al. ¹⁷⁷Lu-PSMA-I&T for treatment of metastatic castration-resistant prostate cancer: prognostic value of scintigraphic and clinical biomarkers. J Nucl Med, 2023, 64(3): 402-409.
25.	Golan S, Frumer M, Zohar Y, et al. Neoadjuvant ¹⁷⁷Lu-PSMA-I&T radionuclide treatment in patients with high-risk prostate cancer before radical prostatectomy: a single-arm phase 1 trial. Eur Urol Oncol, 2023, 6(2): 151-159.
26.	Ruigrok EAM, van Weerden WM, Nonnekens J, et al. The future of PSMA-targeted radionuclide therapy: an overview of recent preclinical research. Pharmaceutics, 2019, 11(11): 560.
27.	Ramnaraign B, Sartor O. PSMA-targeted radiopharmaceuticals in prostate cancer: current data and new trials. Oncologist, 2023, 28(5): 392-401.
28.	张昊, 辛鹏, 张宇曦. ¹⁷⁷Lu-PSMA-617 治疗转移性去势抵抗性前列腺癌有效性和安全性的 meta 分析. 中华男科学杂志, 2021, 27(1): 63-69.
29.	Kim YJ, Kim YI. Therapeutic responses and survival effects of ¹⁷⁷Lu-PSMA-617 radioligand therapy in metastatic castrate-resistant prostate cancer: a meta-analysis. Clin Nucl Med, 2018, 43(10): 728-734.
30.	Violet J, Sandhu S, Iravani A, et al. Long-term follow-up and outcomes of retreatment in an expanded 50-patient single-center phase II prospective trial of ¹⁷⁷Lu-PSMA-617 theranostics in metastatic castration-resistant prostate cancer. J Nucl Med, 2020, 61(6): 857-865.
31.	Hofman MS, Violet J, Hicks RJ, et al. [¹⁷⁷Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol, 2018, 19(6): 825-833.
32.	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.
33.	Garje R, Rumble RB, Parikh RA. Systemic therapy update on ¹⁷⁷Lutetium-PSMA-617 for metastatic castration-resistant prostate cancer: ASCO rapid recommendation. J Clin Oncol, 2022, 40(31): 3664-3666.
34.	Schuchardt C, Zhang J, Kulkarni HR, et al. Prostate-specific membrane antigen radioligand therapy using ¹⁷⁷Lu-PSMA I&T and ¹⁷⁷Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer: comparison of safety, biodistribution, and dosimetry. J Nucl Med, 2022, 63(8): 1199-1207.
35.	Hartrampf PE, Weinzierl FX, Buck AK, et al. Matched-pair analysis of [¹⁷⁷Lu] Lu-PSMA I&T and [¹⁷⁷Lu] Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging, 2022, 49(9): 3269-3276.
36.	Feuerecker B, Tauber R, Knorr K, et al. Activity and adverse events of actinium-225-PSMA-617 in advanced metastatic castration-resistant prostate cancer after failure of Lutetium-177-PSMA. Eur Urol, 2021, 79(3): 343-350.
37.	Ballal S, Yadav MP, Sahoo RK, et al. ²²⁵Ac-PSMA-617-targeted alpha therapy for the treatment of metastatic castration-resistant prostate cancer: a systematic review and meta-analysis. Prostate, 2021, 81(9): 580-591.
38.	Khreish F, Ebert N, Ries M, et al. ²²⁵Ac-PSMA-^617/177Lu-PSMA-617 tandem therapy of metastatic castration-resistant prostate cancer: pilot experience. Eur J Nucl Med Mol Imaging, 2020, 47(3): 721-728.
39.	Yilmaz B, Nisli S, Ergul N, et al. Effect of external cooling on ¹⁷⁷Lu-PSMA uptake by the parotid glands. J Nucl Med, 2019, 60(10): 1388-1393.
40.	Nail V, Louis B, Moyon A, et al. Sublingual atropine administration as a tool to decrease salivary glands’ PSMA-ligand uptake: a preclinical proof of concept study using [⁶⁸Ga] Ga-PSMA-11. Pharmaceutics, 2022, 14(6): 1276.
41.	Jacoba IM, Weber HC. Biomarkers in gastroenteropancreatic neuroendocrine neoplasms. Curr Opin Endocrinol Diabetes Obes, 2023, 30(3): 175-180.
42.	Fernandes CJ, Leung G, Eads JR, et al. Gastroenteropancreatic neuroendocrine tumors. Gastroenterol Clin North Am, 2022, 51(3): 625-647.
43.	中华医学会病理学分会消化疾病学组, 2020 年中国胃肠胰神经内分泌肿瘤病理诊断共识专家组. 中国胃肠胰神经内分泌肿瘤病理诊断共识(2020 版). 中华病理学杂志, 2021, 50(1): 14-20.
44.	杨晓冉, 杨欢, 闫慧姣, 等. 2001-2010 年中国胃肠胰神经内分泌癌临床流行病学研究. 中国肿瘤, 2021, 30(1): 74-80.
45.	Theodoropoulou M, Stalla GK. Somatostatin receptors: from signaling to clinical practice. Front Neuroendocrinol, 2013, 34(3): 228-252.
46.	Geenen L, Nonnekens J, Konijnenberg M, et al. Overcoming nephrotoxicity in peptide receptor radionuclide therapy using [¹⁷⁷Lu] Lu-DOTA-TATE for the treatment of neuroendocrine tumours. Nucl Med Biol, 2021, 102-103: 1-11.
47.	Hendifar AE, Mehr SH, McHaffie DR. Best practices for the coordinated care of patients with neuroendocrine tumors undergoing peptide receptor radionuclide therapy. Pancreas, 2022, 51(3): 213-218.
48.	Das S, Al-Toubah T, El-Haddad G, et al. ¹⁷⁷Lu-DOTATATE for the treatment of gastroenteropancreatic neuroendocrine tumors. Expert Rev Gastroenterol Hepatol, 2019, 13(11): 1023-1031.
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1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. 中国共产党中央委员会, 中华人民共和国国务院. “健康中国 2030”规划纲要. 中国肿瘤, 2019(10): 724.
3. 卓连刚, 杨宇川, 岳海东, 等. DGA 树脂辅助的循环淋洗技术制备无载体镥[¹⁷⁷Lu]. 同位素, 2022, 35(3): 217-223.
4. 杨宇川, 阚文涛, 杨夏, 等. ¹⁷⁷Lu 放射性治疗药物研究新进展. 同位素, 2022, 35(3): 164-178.
5. 张朋俊, 张露露, 卜婷, 等. ¹⁷⁷Lu 标记的放射性药物制备方法的比较及初步临床应用. 中华核医学与分子影像杂志, 2022, 42(10): 597-601.
6. Zakaly HMH, Mostafa MYA, Deryabina D, et al. Comparative studies on the potential use of ¹⁷⁷Lu-based radiopharmaceuticals for the palliative therapy of bone metastases. Int J Radiat Biol, 2020, 96(6): 779-789.
7. 冯婷婷, 成伟华, 王斌, 等. ¹⁷⁷Lu 标记放射性药物临床研究进展. 标记免疫分析与临床, 2018, 25(11): 1750-1756.
8. Heston WD. Characterization and glutamyl preferring carboxypeptidase function of prostate specific membrane antigen: a novel folate hydrolase. Urology, 1997, 49(Suppl 3A): 104-112.
9. Boegemann M, Schrader AJ, Rahbar K. ¹⁷⁷Lu-PSMA therapy : current evidence for use in the treatment of patients with metastatic prostate cancer. Urologe A, 2017, 56(11): 1440-1444.
10. Ghosh A, Heston WD. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem, 2004, 91(3): 528-539.
11. Miller KD, Nogueira L, Devasia T, et al. Cancer treatment and survivorship statistics, 2022. CA Cancer J Clin, 2022, 72(5): 409-436.
12. Zeng H, Chen W, Zheng R, et al. Changing cancer survival in China during 2003-15: a pooled analysis of 17 population-based cancer registries. Lancet Glob Health, 2018, 6(5): e555-e567.
13. Achard V, Panje CM, Engeler D, et al. Localized and locally advanced prostate cancer: treatment options. Oncology, 2021, 99(7): 413-421.
14. Desai K, McManus JM, Sharifi N. Hormonal therapy for prostate cancer. Endocr Rev, 2021, 42(3): 354-373.
15. Schaeffer EM, Srinivas S, Adra N, et al. NCCN guidelines^® insights: prostate cancer, version 1.2023. J Natl Compr Canc Netw, 2022, 20(12): 1288-1298.
16. Naseer F, Ahmad T, Kousar K, et al. Advanced therapeutic options for treatment of metastatic castration resistant prostatic adenocarcinoma. Front Pharmacol, 2021, 12: 728054.
17. Cao J, Chen Y, Hu M, et al. ¹⁷⁷Lu-PSMA-RLT of metastatic castration-resistant prostate cancer: limitations and improvements. Ann Nucl Med, 2021, 35(8): 861-870.
18. Sadaghiani MS, Sheikhbahaei S, Werner RA, et al. ¹⁷⁷Lu-PSMA radioligand therapy effectiveness in metastatic castration-resistant prostate cancer: an updated systematic review and meta-analysis. Prostate, 2022, 82(7): 826-835.
19. 谢彦, 李澄, 张露露, 等. ¹⁷⁷Lu-PSMA-I&T 治疗前列腺癌的疗效评价. 中华核医学与分子影像杂志, 2021, 41(6): 356-361.
20. Weineisen M, Schottelius M, Simecek J, et al. ⁶⁸Ga- and ¹⁷⁷Lu-labeled PSMA I&T: optimization of a PSMA-targeted theranostic concept and first proof-of-concept human studies. J Nucl Med, 2015, 56(8): 1169-1176.
21. Barna S, Haug AR, Hartenbach M, et al. Dose calculations and dose-effect relationships in ¹⁷⁷Lu-PSMA I&T radionuclide therapy for metastatic castration-resistant prostate cancer. Clin Nucl Med, 2020, 45(9): 661-667.
22. Hartrampf PE, Weinzierl FX, Serfling SE, et al. Hematotoxicity and nephrotoxicity in prostate cancer patients undergoing radioligand therapy with [¹⁷⁷Lu] Lu-PSMA I&T. Cancers (Basel), 2022, 14(3): 647.
23. Bu T, Zhang L, Yu F, et al. ¹⁷⁷Lu-PSMA-I&T radioligand therapy for treating metastatic castration-resistant prostate cancer: a single-centre study in East Asians. Front Oncol, 2022, 12: 835956.
24. Karimzadeh A, Heck M, Tauber R, et al. ¹⁷⁷Lu-PSMA-I&T for treatment of metastatic castration-resistant prostate cancer: prognostic value of scintigraphic and clinical biomarkers. J Nucl Med, 2023, 64(3): 402-409.
25. Golan S, Frumer M, Zohar Y, et al. Neoadjuvant ¹⁷⁷Lu-PSMA-I&T radionuclide treatment in patients with high-risk prostate cancer before radical prostatectomy: a single-arm phase 1 trial. Eur Urol Oncol, 2023, 6(2): 151-159.
26. Ruigrok EAM, van Weerden WM, Nonnekens J, et al. The future of PSMA-targeted radionuclide therapy: an overview of recent preclinical research. Pharmaceutics, 2019, 11(11): 560.
27. Ramnaraign B, Sartor O. PSMA-targeted radiopharmaceuticals in prostate cancer: current data and new trials. Oncologist, 2023, 28(5): 392-401.
28. 张昊, 辛鹏, 张宇曦. ¹⁷⁷Lu-PSMA-617 治疗转移性去势抵抗性前列腺癌有效性和安全性的 meta 分析. 中华男科学杂志, 2021, 27(1): 63-69.
29. Kim YJ, Kim YI. Therapeutic responses and survival effects of ¹⁷⁷Lu-PSMA-617 radioligand therapy in metastatic castrate-resistant prostate cancer: a meta-analysis. Clin Nucl Med, 2018, 43(10): 728-734.
30. Violet J, Sandhu S, Iravani A, et al. Long-term follow-up and outcomes of retreatment in an expanded 50-patient single-center phase II prospective trial of ¹⁷⁷Lu-PSMA-617 theranostics in metastatic castration-resistant prostate cancer. J Nucl Med, 2020, 61(6): 857-865.
31. Hofman MS, Violet J, Hicks RJ, et al. [¹⁷⁷Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol, 2018, 19(6): 825-833.
32. 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.
33. Garje R, Rumble RB, Parikh RA. Systemic therapy update on ¹⁷⁷Lutetium-PSMA-617 for metastatic castration-resistant prostate cancer: ASCO rapid recommendation. J Clin Oncol, 2022, 40(31): 3664-3666.
34. Schuchardt C, Zhang J, Kulkarni HR, et al. Prostate-specific membrane antigen radioligand therapy using ¹⁷⁷Lu-PSMA I&T and ¹⁷⁷Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer: comparison of safety, biodistribution, and dosimetry. J Nucl Med, 2022, 63(8): 1199-1207.
35. Hartrampf PE, Weinzierl FX, Buck AK, et al. Matched-pair analysis of [¹⁷⁷Lu] Lu-PSMA I&T and [¹⁷⁷Lu] Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging, 2022, 49(9): 3269-3276.
36. Feuerecker B, Tauber R, Knorr K, et al. Activity and adverse events of actinium-225-PSMA-617 in advanced metastatic castration-resistant prostate cancer after failure of Lutetium-177-PSMA. Eur Urol, 2021, 79(3): 343-350.
37. Ballal S, Yadav MP, Sahoo RK, et al. ²²⁵Ac-PSMA-617-targeted alpha therapy for the treatment of metastatic castration-resistant prostate cancer: a systematic review and meta-analysis. Prostate, 2021, 81(9): 580-591.
38. Khreish F, Ebert N, Ries M, et al. ²²⁵Ac-PSMA-^617/177Lu-PSMA-617 tandem therapy of metastatic castration-resistant prostate cancer: pilot experience. Eur J Nucl Med Mol Imaging, 2020, 47(3): 721-728.
39. Yilmaz B, Nisli S, Ergul N, et al. Effect of external cooling on ¹⁷⁷Lu-PSMA uptake by the parotid glands. J Nucl Med, 2019, 60(10): 1388-1393.
40. Nail V, Louis B, Moyon A, et al. Sublingual atropine administration as a tool to decrease salivary glands’ PSMA-ligand uptake: a preclinical proof of concept study using [⁶⁸Ga] Ga-PSMA-11. Pharmaceutics, 2022, 14(6): 1276.
41. Jacoba IM, Weber HC. Biomarkers in gastroenteropancreatic neuroendocrine neoplasms. Curr Opin Endocrinol Diabetes Obes, 2023, 30(3): 175-180.
42. Fernandes CJ, Leung G, Eads JR, et al. Gastroenteropancreatic neuroendocrine tumors. Gastroenterol Clin North Am, 2022, 51(3): 625-647.
43. 中华医学会病理学分会消化疾病学组, 2020 年中国胃肠胰神经内分泌肿瘤病理诊断共识专家组. 中国胃肠胰神经内分泌肿瘤病理诊断共识(2020 版). 中华病理学杂志, 2021, 50(1): 14-20.
44. 杨晓冉, 杨欢, 闫慧姣, 等. 2001-2010 年中国胃肠胰神经内分泌癌临床流行病学研究. 中国肿瘤, 2021, 30(1): 74-80.
45. Theodoropoulou M, Stalla GK. Somatostatin receptors: from signaling to clinical practice. Front Neuroendocrinol, 2013, 34(3): 228-252.
46. Geenen L, Nonnekens J, Konijnenberg M, et al. Overcoming nephrotoxicity in peptide receptor radionuclide therapy using [¹⁷⁷Lu] Lu-DOTA-TATE for the treatment of neuroendocrine tumours. Nucl Med Biol, 2021, 102-103: 1-11.
47. Hendifar AE, Mehr SH, McHaffie DR. Best practices for the coordinated care of patients with neuroendocrine tumors undergoing peptide receptor radionuclide therapy. Pancreas, 2022, 51(3): 213-218.
48. Das S, Al-Toubah T, El-Haddad G, et al. ¹⁷⁷Lu-DOTATATE for the treatment of gastroenteropancreatic neuroendocrine tumors. Expert Rev Gastroenterol Hepatol, 2019, 13(11): 1023-1031.
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Current application of ¹⁷⁷Lu in solid tumors

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Current application of ¹⁷⁷Lu in solid tumors