Institute for Environment, Health and Safety, Radiobiology Unit, Belgian Nuclear Research Centre (SCK CEN), Mol, Belgium; Department of Molecular Biotechnology, Ghent University, Ghent, Belgium.
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America; Department of Nuclear Medicine, Medical Faculty, University Hospital Essen, Essen, Germany.
Nucl Med Biol. 2021 Jul-Aug;98-99:30-39. doi: 10.1016/j.nucmedbio.2021.04.003. Epub 2021 May 8.
At present, prostate cancer remains the second most occurring cancer in men, in Europe. Treatment efficacy for therapy of advanced metastatic disease, and metastatic castration-resistant prostate cancer in particular is limited. Prostate-specific membrane antigen (PSMA) is a promising therapeutic target in prostate cancer, seeing the high amount of overexpression on prostate cancer cells. Clinical investigation of PSMA-targeted radionuclide therapy has shown good clinical efficacy. However, adverse effects are observed of which salivary gland hypofunction and xerostomia are among the most prominent. Salivary gland toxicity is currently the dose-limiting side effect for PSMA-targeted radionuclide therapy, and more specifically for PSMA-targeted alpha therapy. To date, mechanisms underlying the salivary gland uptake of PSMA-targeting compounds and the subsequent damage to the salivary glands remain largely unknown. Furthermore, preventive strategies for salivary gland uptake or strategies for treatment of salivary gland toxicity are needed. This review focuses on the current knowledge on uptake mechanisms of PSMA-targeting compounds in the salivary glands and the research performed to investigate different strategies to prevent or treat salivary gland toxicity.
目前，前列腺癌仍是欧洲男性第二大常见癌症。对于晚期转移性疾病，特别是转移性去势抵抗性前列腺癌的治疗效果有限。前列腺特异性膜抗原（PSMA）是前列腺癌中一种很有前途的治疗靶点，因为其在前列腺癌细胞上过度表达。针对 PSMA 的放射性核素治疗的临床研究已显示出良好的临床疗效。然而，也观察到了不良反应，其中唾液腺功能减退和口干是最突出的。唾液腺毒性是目前 PSMA 靶向放射性核素治疗，特别是 PSMA 靶向α治疗的剂量限制副作用。迄今为止，PSMA 靶向化合物在唾液腺中的摄取机制以及随后对唾液腺的损伤在很大程度上仍不清楚。此外，需要预防唾液腺摄取的策略或治疗唾液腺毒性的策略。这篇综述重点介绍了目前关于 PSMA 靶向化合物在唾液腺中摄取机制的知识，以及为研究预防或治疗唾液腺毒性的不同策略而进行的研究。
