替代 ⁸⁹Zr 放射性药物的螯合剂：3,4,3-(LI-1,2-HOPO)的放射性标记和评估。

Alternative chelator for ⁸⁹Zr radiopharmaceuticals: radiolabeling and evaluation of 3,4,3-(LI-1,2-HOPO).

机构信息

Department of Radiology and the Program in Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center , 1275 York Avenue, New York, New York 10065, United States.

出版信息

J Med Chem. 2014 Jun 12;57(11):4849-60. doi: 10.1021/jm500389b. Epub 2014 May 19.

DOI:10.1021/jm500389b

PMID:24814511

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4059252/

Abstract

Zirconium-89 is an effective radionuclide for antibody-based positron emission tomography (PET) imaging because its physical half-life (78.41 h) matches the biological half-life of IgG antibodies. Desferrioxamine (DFO) is currently the preferred chelator for (89)Zr(4+); however, accumulation of (89)Zr in the bones of mice suggests that (89)Zr(4+) is released from DFO in vivo. An improved chelator for (89)Zr(4+) could eliminate the release of osteophilic (89)Zr(4+) and lead to a safer PET tracer with reduced background radiation dose. Herein, we present an octadentate chelator 3,4,3-(LI-1,2-HOPO) (or HOPO) as a potentially superior alternative to DFO. The HOPO ligand formed a 1:1 Zr-HOPO complex that was evaluated experimentally and theoretically. The stability of (89)Zr-HOPO matched or surpassed that of (89)Zr-DFO in every experiment. In healthy mice, (89)Zr-HOPO cleared the body rapidly with no signs of demetalation. Ultimately, HOPO has the potential to replace DFO as the chelator of choice for (89)Zr-based PET imaging agents.

摘要

锆-89 是一种有效的放射性核素，可用于基于抗体的正电子发射断层扫描（PET）成像，因为其物理半衰期（78.41 小时）与 IgG 抗体的生物半衰期相匹配。去铁胺（DFO）目前是（89）Zr（4+）的首选螯合剂；然而，（89）Zr 在小鼠骨骼中的积累表明，（89）Zr（4+）在体内从 DFO 中释放出来。对于（89）Zr（4+）的改进螯合剂可以消除亲骨性（89）Zr（4+）的释放，并导致具有更低背景辐射剂量的更安全的 PET 示踪剂。在此，我们提出了一种八齿螯合剂 3,4,3-（LI-1,2-HOPO）（或 HOPO），作为 DFO 的潜在替代品。HOPO 配体形成了 1:1 的 Zr-HOPO 配合物，该配合物已通过实验和理论进行了评估。（89）Zr-HOPO 的稳定性在每个实验中都与（89）Zr-DFO 相匹配或超过（89）Zr-DFO。在健康小鼠中，（89）Zr-HOPO 迅速清除体内，没有脱金属迹象。最终，HOPO 有可能取代 DFO 作为（89）Zr 基 PET 成像剂的螯合剂。