Alam Mohammad R, Singh Shashi B, Thapaliya Shreeya, Shrestha Shreeya, Deo Sulav, Khanal Kishor
Department of Internal Medicine, Argakhachi Hospital Pvt. Ltd, Sandhikharka, NPL.
Department of Radiology, KIST Medical College and Teaching Hospital, Kathmandu, NPL.
Cureus. 2022 Sep 20;14(9):e29369. doi: 10.7759/cureus.29369. eCollection 2022 Sep.
The development of prostate-specific membrane antigen (PSMA) ligands labeled with radionuclides is a ground-breaking achievement in the management of prostate cancer. With the increasing use of Gallium-PSMA and F-DCFPyL (Pylarify) and their approval by the Food and Drug Administration (FDA), other PSMA agents and their unique characteristics are also being studied. Two other PSMA agents, namely Lutetium-PSMA (Lu-PSMA) and Actinium-PSMA (Ac-PSMA), are currently drawing the researcher's attention mainly due to their theranostic importance. Studies focusing on the essential characteristics of these two emerging radiotracers are relatively lacking. Hence, this review article, beginning with a brief introduction, intends to provide insights on the mechanism, efficacy, adverse effects, usefulness, including theranostic implications, and limitations of these two emerging PSMA agents. The Lu-PSMA is commercially accessible, is well tolerated, and has been found to lower prostate-specific antigen (PSA) levels while improving patients' quality of life. It also reduces pain and the requirement for analgesics and is safe for advanced diseases. However, despite its potential advantages, around one-third of patients do not respond satisfactorily to this costly treatment; it is still challenging to personalize this therapy and predict its outcome. Similarly, Ac is compatible with antibody-based targeting vectors, releasing four extremely hazardous high-energy emissions with a longer half-life of 10 days. It has made Ac-PSMA therapy useful for tumors resistant to standard treatments, with a better response than Lu-PSMA. Dosimetry studies show a good biochemical response without toxicity in patients with advanced metastatic castration-resistant prostate cancer (mCRPC). However, it can potentially cause significant damage to healthy tissues if not retained at the tumor site. Encapsulating radionuclides in a nano-carrier, hastening the absorption by tumor cells, and local delivery might all help reduce the harmful consequences. Both have advantages and disadvantages. The choice of PSMA agents may rely on desired qualities, cost, and convenience, among other factors. Further research is warranted in order to better understand their ideal use in clinical settings.
放射性核素标记的前列腺特异性膜抗原（PSMA）配体的研发是前列腺癌治疗领域的一项突破性成就。随着镓-PSMA和F-DCFPyL（Pylarify）的使用日益增加并获得美国食品药品监督管理局（FDA）的批准，其他PSMA制剂及其独特特性也在研究之中。另外两种PSMA制剂，即镥-PSMA（Lu-PSMA）和锕-PSMA（Ac-PSMA），目前因其在治疗诊断方面的重要性而备受研究人员关注。针对这两种新兴放射性示踪剂基本特性的研究相对较少。因此，这篇综述文章首先进行简要介绍，旨在深入探讨这两种新兴PSMA制剂的作用机制、疗效、不良反应、用途（包括治疗诊断意义）及局限性。Lu-PSMA已商业化可得，耐受性良好，已发现其能降低前列腺特异性抗原（PSA）水平，同时改善患者生活质量。它还能减轻疼痛并减少止痛药物的需求，对晚期疾病也很安全。然而，尽管其具有潜在优势，但约三分之一的患者对这种昂贵治疗的反应并不理想；个性化这种治疗并预测其结果仍具有挑战性。同样，锕与基于抗体的靶向载体兼容，会释放四种极具危险性的高能辐射，半衰期较长，为10天。这使得Ac-PSMA疗法对耐药肿瘤有效，反应比Lu-PSMA更好。剂量学研究表明，晚期转移性去势抵抗性前列腺癌（mCRPC）患者在无毒性的情况下有良好的生化反应。然而，如果不能在肿瘤部位留存，它可能会对健康组织造成严重损害。将放射性核素封装在纳米载体中，加速肿瘤细胞吸收以及进行局部递送，可能都有助于减少有害影响。两者都有优缺点。PSMA制剂的选择可能取决于所需特性、成本和便利性等诸多因素。有必要进一步开展研究，以便更好地了解它们在临床环境中的理想应用。
