Bakht Martin K, Oh So Won, Youn Hyewon, Cheon Gi Jeong, Kwak Cheol, Kang Keon Wook
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, 110-744 Korea.
Laboratory of Molecular Imaging and Therapy, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Nucl Med Mol Imaging. 2017 Sep;51(3):202-211. doi: 10.1007/s13139-016-0439-4. Epub 2016 Aug 6.
Prostate-specific membrane antigen (PSMA) is an attractive target for both diagnosis and therapy because of its high expression in the vast majority of prostate cancers. Development of small molecules for targeting PSMA is important for molecular imaging and radionuclide therapy of prostate cancer. Recent evidence implies that androgen-deprivation therapy increase PSMA-ligand uptake in some cases. The reported upregulations in PSMA-ligand uptake after exposure to second-generation antiandrogens such as enzalutamide and abiraterone might disturb PSMA-targeted imaging for staging and response monitoring of patients undergoing treatment with antiandrogen-based drugs. On the other hand, second-generation antiandrogens are emerging as potential endoradio-/chemosensitizers. Therefore, the enhancement of the therapeutic efficiency of PSMA-targeted theranostic methods can be listed as a new capability of antiandrogens. In this manuscript, we will present what is currently known about the mechanism of increasing PSMA uptake following exposure to antiandrogens. In addition, we will discuss whether these above-mentioned antiandrogens could play the role of endoradio-/chemosensitizers in combination with the well-established PSMA-targeted methods for pre-targeting of prostate cancer.
前列腺特异性膜抗原（PSMA）因其在绝大多数前列腺癌中高表达，成为诊断和治疗的一个有吸引力的靶点。开发靶向PSMA的小分子对于前列腺癌的分子成像和放射性核素治疗很重要。最近的证据表明，在某些情况下雄激素剥夺疗法会增加PSMA配体摄取。据报道，在接触恩杂鲁胺和阿比特龙等第二代抗雄激素药物后，PSMA配体摄取上调，这可能会干扰接受抗雄激素类药物治疗患者的PSMA靶向成像用于分期和反应监测。另一方面，第二代抗雄激素药物正成为潜在的内照射/化学增敏剂。因此，提高PSMA靶向诊疗方法的治疗效率可列为抗雄激素药物的一项新功能。在本手稿中，我们将阐述目前已知的接触抗雄激素药物后PSMA摄取增加的机制。此外，我们将讨论上述抗雄激素药物与成熟的前列腺癌预靶向PSMA靶向方法联合使用时，是否能发挥内照射/化学增敏剂的作用。
