Tomiyoshi Katsumi, Wilson Lydia J, Mourtada Firas, Mourtada Jennifer Sims, Namiki Yuta, Kamata Wataru, Yang David J, Inoue Tomio
Shonan Research Institute of Innovative Medicine, Shonan Kamakura General Hospital, Kamakura 247-8533, Japan.
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Pharmaceutics. 2024 Nov 15;16(11):1458. doi: 10.3390/pharmaceutics16111458.
Targeted radionuclide therapy (TRT) for internal pathway-directed treatment is a game changer for precision medicine. TRT improves tumor control while minimizing damage to healthy tissue and extends the survival for patients with cancer. The application of theranostic-paired TRT along with cellular phenotype and genotype correlative analysis has the potential for malignant disease management. Chelation chemistry is essential for the development of theranostic-paired radiopharmaceuticals for TRT. Among image-guided TRT, Ga and Tc are the current standards for diagnostic radionuclides, while Lu and Ac have shown great promise for β- and α-TRT, respectively. Their long half-lives, potent radiobiology, favorable decay schemes, and ability to form stable chelation conjugates make them ideal for both manufacturing and clinical use. The current challenges include optimizing radionuclide production processes, coordinating chelation chemistry stability of theranostic-paired isotopes to reduce free daughters [this pertains to Ac daughters Fr and Bi]-induced tissue toxicity, and improving the modeling of micro dosimetry to refine dose-response evaluation. The empirical approach to TRT delivery is based on standard radionuclide administered activity levels, although clinical trials have revealed inconsistent outcomes and normal-tissue toxicities despite equivalent administered activities. This review presents the latest optimization methods for chelation-based theranostic radiopharmaceuticals, advancements in micro-dosimetry, and SPECT/CT technologies for quantifying whole-body uptake and monitoring therapeutic response as well as cytogenetic correlative analyses.
用于内照射途径导向治疗的靶向放射性核素疗法（TRT）是精准医学的一个变革者。TRT提高了肿瘤控制效果，同时将对健康组织的损害降至最低，并延长了癌症患者的生存期。治疗诊断配对的TRT与细胞表型和基因型相关分析的应用在恶性疾病管理方面具有潜力。螯合化学对于开发用于TRT的治疗诊断配对放射性药物至关重要。在图像引导的TRT中，Ga和Tc是目前诊断放射性核素的标准，而Lu和Ac分别在β-TRT和α-TRT方面显示出巨大潜力。它们的长半衰期、强大的放射生物学特性、良好的衰变方案以及形成稳定螯合共轭物的能力使其非常适合制造和临床应用。当前的挑战包括优化放射性核素生产工艺、协调治疗诊断配对同位素的螯合化学稳定性以减少游离子体[这与Ac子体Fr和Bi有关]诱导的组织毒性，以及改进微剂量学模型以完善剂量反应评估。TRT给药的经验方法基于标准放射性核素给药活度水平，尽管临床试验表明，尽管给药活度相同，但结果和正常组织毒性并不一致。本综述介绍了基于螯合的治疗诊断放射性药物的最新优化方法、微剂量学的进展以及用于量化全身摄取和监测治疗反应的SPECT/CT技术以及细胞遗传学相关分析。
