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一个一流的双化器治疗剂,旨在用于不同元素的成像治疗放射性金属对

James L Wood^1,2, Saikat Ghosh², Zachary H Houston²

¹The University of Sydney, School of Medical Sciences New South Wales 2006 Australia rachel.codd@sydney.edu.au.

Chemical science

|August 2, 2024

概括

这项研究引入了一种双化器治疗剂DFOB-l-Lys-N6-DOTA,可同时对不同放射性金属进行成像和治疗. 这种新药在临床前模型中表现出有效的瘤向和治疗疗效.

科学领域:

核医学是一种核医学.
放射性药物化学放射性药物化学
在瘤学瘤学.

背景情况:

治疗术结合了诊断成像和向治疗.
开发双器系统允许灵活使用不同的放射性金属用于成像和治疗.
现有的异能剂可能在放射性金属兼容性或准效率方面存在局限性.

研究的目的:

设计和评估一种新的三功能化剂 (D2),用于混合元素放射性金属化学.
评估使用D2同时用于正子发射断层扫描 (PET) 成像和向放射性核酸治疗的可行性.
为了研究 D2 结合抗体对前列腺癌的 vivo 性能.

主要方法:

合成DFOB-l-Lys-N6-DOTA及其PEGylated衍生物 (D2) 用于抗体结合.
D2结合抗体 (HuJ591) 的放射性标记,用于PET成像的89Zr和治疗的177Lu.
在小鼠LNCaP前列腺瘤异种移植模型的体内评估,使用PET/CT和SPECT/CT成像,以及生物分布研究.

主要成果:

双器D2表现出对Zr (iv) 和Lu (iii) 的区域选择性金属结合.
89Zr-免疫-PET成像显示D2-mAb和对照DFOB-mAb的瘤积累可比较.
[¹⁷⁷Lu]Lu-D2-mAb显示出显著的瘤吸收和治疗疗效,与[¹⁷⁷Lu]Lu-DOTA-mAb相比,瘤体积减少>80%.

结论:

D2是一种多用途的三功能化剂,可实现混合元素放射性金属化学.
这种方法扩大了光学能力,有可能改善分子向放射治疗中的剂量测量和临床结果.
D2-mAb构造显示未来前列腺癌治疗中的临床转化有希望.

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