Radiological Physics Division, Department of Radiology, Johns Hopkins University, School of Medicine, Baltimore, MD.
Semin Nucl Med. 2020 Mar;50(2):124-132. doi: 10.1053/j.semnuclmed.2019.11.002. Epub 2020 Feb 26.
As a treatment modality that is fundamentally different from other therapies against cancer, radiopharmaceutical therapy with alpha-particle emitters has drawn the attention of the therapy community and also the biopharmaceutical industry. Alpha-particles cause a preponderance of complex DNA double-strand breaks (DSBs). This provides an opportunity to either enhance cell kill by using DNA DSB repair inhibitors or identify patients who are likely to be high responders to alpha-emitter RPT. The short-range and high potency of alpha-particles requires special dosimetry considerations. These are reviewed in light of recent updates to the phantoms and associated dosimetric quantities used for dosimetry calculations. A formalism for obtaining the necessary microscale pharmacokinetic information from patient nuclear medicine imaging is presented. Alpha-emitter based radiopharmaceutical therapy is an exciting cancer therapy modality that is being revisited. Further development of imaging and dosimetric methods specific to alpha-particle emitters, coupled with standardization of the methods and rigorous evidence that dosimetry applied to alphaRPT improves patient care are needed moving forward.
作为一种与其他癌症治疗方法在根本上不同的治疗方式，放射性药物治疗与α粒子发射体引起了治疗界和生物制药行业的关注。α粒子会导致大量复杂的 DNA 双链断裂（DSBs）。这为使用 DNA DSB 修复抑制剂增强细胞杀伤提供了机会，或者识别出可能对α发射体 RPT 有高反应的患者。α粒子的短射程和高能量需要特殊的剂量学考虑。鉴于最近对用于剂量计算的体模和相关剂量学量的更新，对这些考虑因素进行了回顾。提出了一种从患者核医学成像中获得必要微观药代动力学信息的形式主义方法。基于α发射体的放射性药物治疗是一种令人兴奋的癌症治疗方式，正在重新受到关注。需要进一步开发针对α粒子发射体的成像和剂量学方法，并结合方法的标准化以及严格的证据，即应用于αRPT 的剂量学可改善患者护理。
