走向用于核医学的钪放射性同位素配合物的临床开发:用螯合剂 1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(DOTA)及其类似物带来的可喜前景。

Towards Clinical Development of Scandium Radioisotope Complexes for Use in Nuclear Medicine: Encouraging Prospects with the Chelator 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic Acid (DOTA) and Its Analogues.

机构信息

Department of Chemistry, University of Cyprus, 2109 Nicosia, Cyprus.

Postgraduate Research Institute of Science, Technology, Environment and Medicine, 3021 Limassol, Cyprus.

出版信息

Int J Mol Sci. 2024 May 29;25(11):5954. doi: 10.3390/ijms25115954.

Abstract

Scandium (Sc) isotopes have recently attracted significant attention in the search for new radionuclides with potential uses in personalized medicine, especially in the treatment of specific cancer patient categories. In particular, Sc-43 and Sc-44, as positron emitters with a satisfactory half-life (3.9 and 4.0 h, respectively), are ideal for cancer diagnosis via Positron Emission Tomography (PET). On the other hand, Sc-47, as an emitter of beta particles and low gamma radiation, may be used as a therapeutic radionuclide, which also allows Single-Photon Emission Computed Tomography (SPECT) imaging. As these scandium isotopes follow the same biological pathway and chemical reactivity, they appear to fit perfectly into the "theranostic pair" concept. A step-by-step description, initiating from the moment of scandium isotope production and leading up to their preclinical and clinical trial applications, is presented. Recent developments related to the nuclear reactions selected and employed to produce the radionuclides Sc-43, Sc-44, and Sc-47, the chemical processing of these isotopes and the main target recovery methods are also included. Furthermore, the radiolabeling of the leading chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and its structural analogues with scandium is also discussed and the advantages and disadvantages of scandium complexation are evaluated. Finally, a review of the preclinical studies and clinical trials involving scandium, as well as future challenges for its clinical uses and applications, are presented.

摘要

钪(Sc)同位素最近在寻找具有潜在个性化医学用途的新放射性核素方面引起了广泛关注,特别是在治疗特定癌症患者群体方面。特别是,作为正电子发射体的 Sc-43 和 Sc-44,半衰期分别为 3.9 和 4.0 小时,是通过正电子发射断层扫描(PET)进行癌症诊断的理想选择。另一方面,Sc-47 作为β粒子和低伽马辐射的发射器,可能被用作治疗性放射性核素,这也允许单光子发射计算机断层扫描(SPECT)成像。由于这些钪同位素遵循相同的生物学途径和化学反应性,它们似乎非常适合“治疗诊断对”的概念。本文从钪同位素的生产开始,逐步描述了它们在临床前和临床试验中的应用。还包括与所选核反应和用于生产放射性核素 Sc-43、Sc-44 和 Sc-47 的化学处理以及主要目标回收方法相关的最新发展。此外,还讨论了钪的主要螯合剂 1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(DOTA)及其与钪的结构类似物的放射性标记,并评估了钪络合物的优缺点。最后,介绍了涉及钪的临床前研究和临床试验以及未来其临床应用和应用的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79ba/11173192/3609001cf223/ijms-25-05954-g008.jpg

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