Kairemo Kalevi, Kgatle Mankgopo, Bruchertseifer Frank, Morgernstern Alfred, Sathekge Mike M
Departments of Molecular Radiotherapy & Nuclear Medicine, Docrates Cancer Center, Helsinki, Finland.
Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ann Transl Med. 2024 Aug 1;12(4):67. doi: 10.21037/atm-23-1842. Epub 2024 Mar 6.
The first alpha emitting radiopharmaceutical, RaCl, radium dichloride, was approved 10 years ago into the clinical armament of treating bone metastases in metastatic castration-resistant prostate cancer (mCRPC). In addition to this, the first beta-emitting radionuclide Lu-177 chelated with a prostate-specific membrane antigen (PSMA) compound, got last year its marketing approval for the third line treatment of mCRPC. Therefore, there is great excitement about combining alpha-emitters and prostate cancer targeting PSMA compounds. This review describes the clinical history of alpha-emitting PSMA in treating mCRPC. Here, we present the potential, current status, and opportunities for Ac-PSMA therapy. The work reviews the basic concepts, current treatment outcome, and toxicity, and areas requiring further investigations such as dosimetric aspects in clinical studies covering more than 400 patients. In general, approximately two-thirds of the patients benefit from this third-line therapy. There is also successful evidence of using Ac-PSMA in the second-line of prostate cancer management. The future potential of Ac-PSMA therapy and targeted alpha therapy (TAT) of cancer in general is enormous. According to our overview the clinical experience with Ac-PSMA therapy to date has shown great benefit and physicians dedicated to theragnostics are anxiously waiting for new applications. Hopefully, this review helps in deeper understanding of the strengths and limitations of TAT and may help in creating effective therapy protocols.
首个发射α粒子的放射性药物二氯化镭（RaCl）于10年前获批用于转移性去势抵抗性前列腺癌（mCRPC）骨转移的临床治疗。除此之外，首个与前列腺特异性膜抗原（PSMA）化合物螯合的发射β粒子的放射性核素镥-177（Lu-177）于去年获批用于mCRPC的三线治疗。因此，将发射α粒子的药物与靶向前列腺癌的PSMA化合物相结合备受关注。本综述描述了发射α粒子的PSMA在治疗mCRPC方面的临床应用历程。在此，我们介绍锕-PSMA（Ac-PSMA）疗法的潜力、现状及机遇。这项工作回顾了基本概念、当前的治疗效果和毒性，以及在涵盖400多名患者的临床研究中剂量学等需要进一步研究的领域。总体而言，约三分之二的患者受益于这种三线治疗。也有在前列腺癌二线治疗中使用Ac-PSMA的成功证据。Ac-PSMA疗法以及一般意义上的癌症靶向α疗法（TAT）未来潜力巨大。根据我们的综述，迄今为止Ac-PSMA疗法的临床经验已显示出巨大益处，致力于诊疗一体化的医生们正急切期待新的应用。希望本综述有助于更深入地理解TAT的优势和局限性，并可能有助于制定有效的治疗方案。
