Mahajan Sonia, Grewal Ravinder K, Friedman Kent P, Schöder Heiko, Pandit-Taskar Neeta
Nuclear Medicine, Department of Radiology, New York University Grossman School of Medicine, New York, NY, United States of America.
Molecular Imaging & Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America.
Transl Oncol. 2022 Jul;21:101445. doi: 10.1016/j.tranon.2022.101445. Epub 2022 May 3.
Prostate specific membrane antigen (PSMA) is a transmembrane protein that is highly expressed on prostate epithelial cells and is strongly upregulated in prostate cancer. Radioligand therapy using beta-emitting Lutetium-177 (Lu)-labeled-PSMA-617, a radiolabeled small molecule, has gained attention as a novel targeted therapy for metastatic prostate cancer, given its high affinity and long tumor retention, and rapid blood pool clearance. In March 2022, the United States Food and Drug administration has granted approval to the targeted Lu-PSMA-617 therapy for treatment of patients with PSMA-positive metastatic castration resistant prostate cancer, who have been previously treated with an androgen-receptor pathway inhibitor and taxane-based chemotherapy. Studies have demonstrated the adverse effects of this treatment, mainly encountered due to radiation exposure to non-target tissues. Salivary glands show high PSMA-ligand uptake and receive increased radiation dose secondary to accumulation of Lu-PSMA-617. This predisposes the glands to radiation-mediated toxicity. The exact mechanism, scope and severity of radiation-mediated salivary gland toxicity are not well understood, however, the strategies for its prevention and treatment are under evaluation. This review will focus on the current knowledge about salivary gland impairment post Lu labeled PSMA-based radioligand therapies, diagnostic methodologies, and imaging with emphasis on salivary gland scintigraphy. The preventive strategies and known treatment options would also be briefly highlighted.
前列腺特异性膜抗原(PSMA)是一种跨膜蛋白,在前列腺上皮细胞上高度表达,在前列腺癌中强烈上调。使用发射β射线的镥-177(Lu)标记的PSMA-617(一种放射性标记的小分子)进行放射性配体治疗,因其高亲和力、长时间的肿瘤滞留和快速的血池清除,作为转移性前列腺癌的一种新型靶向治疗方法受到关注。2022年3月,美国食品药品监督管理局已批准靶向Lu-PSMA-617疗法用于治疗PSMA阳性的转移性去势抵抗性前列腺癌患者,这些患者此前已接受过雄激素受体途径抑制剂和紫杉烷类化疗。研究表明了这种治疗的不良反应,主要是由于非靶组织受到辐射暴露所致。唾液腺显示出高PSMA配体摄取,并因Lu-PSMA-617的积累而接受增加的辐射剂量。这使腺体易发生辐射介导的毒性。然而,辐射介导的唾液腺毒性的确切机制、范围和严重程度尚不清楚,其预防和治疗策略正在评估中。本综述将重点关注基于Lu标记的PSMA放射性配体治疗后唾液腺损伤的现有知识、诊断方法以及成像,重点是唾液腺闪烁显像。预防性策略和已知的治疗选择也将简要强调。