Ruigrok Eline A M, van Weerden Wytske M, Nonnekens Julie, de Jong Marion
Dept. of Radiology and Nuclear Medicine, Erasmus MC, 3015 GD Rotterdam, The Netherlands.
Dept. of Experimental Urology, Erasmus MC, 3015 GD Rotterdam, The Netherlands.
Pharmaceutics. 2019 Oct 29;11(11):560. doi: 10.3390/pharmaceutics11110560.
Prostate specific membrane antigen (PSMA) has become a major focus point in the research and development of prostate cancer (PCa) imaging and therapeutic strategies using radiolabeled tracers. PSMA has shown to be an excellent target for PCa theranostics because of its high expression on the membrane of PCa cells and the increase in expression during disease progression. Therefore, numerous PSMA-targeting tracers have been developed and (pre)clinically studied with promising results. However, many of these PSMA-targeting tracers show uptake in healthy organs such as the salivary glands, causing radiotoxicity. Furthermore, not all patients respond to PSMA-targeted radionuclide therapy (TRT). This created the necessity of additional preclinical research studies in which existing tracers are reevaluated and new tracers are developed in order to improve PSMA-TRT by protecting the (PSMA-expressing) healthy organs and improving tumor uptake. In this review we will give an overview of the recent preclinical research projects regarding PCa-TRT using PSMA-specific radiotracers, which will give an indication of where the PSMA-TRT research movement is going and what we can expect in future clinical trials.
前列腺特异性膜抗原（PSMA）已成为使用放射性标记示踪剂进行前列腺癌（PCa）成像和治疗策略研发的主要焦点。PSMA已被证明是PCa诊疗的一个极佳靶点，因为它在PCa细胞膜上高表达，且在疾病进展过程中表达增加。因此，众多靶向PSMA的示踪剂已被开发并进行了（临床前）研究，结果令人鼓舞。然而，许多这些靶向PSMA的示踪剂在诸如唾液腺等健康器官中也有摄取，从而导致放射性毒性。此外，并非所有患者都对PSMA靶向放射性核素治疗（TRT）有反应。这就产生了进行额外临床前研究的必要性，在这些研究中对现有示踪剂进行重新评估，并开发新的示踪剂，以便通过保护（表达PSMA的）健康器官和提高肿瘤摄取来改进PSMA-TRT。在本综述中，我们将概述近期使用PSMA特异性放射性示踪剂进行PCa-TRT的临床前研究项目，这将表明PSMA-TRT研究的发展方向以及我们在未来临床试验中可以期待什么。
