放射性金属酸盐对免疫检查点蛋白在体内可视化的影响,使用放射性标记的附体分子
Vladimir Tolmachev1, Eleftherios Papalanis1, Ekaterina A Bezverkhniaia2
1Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden.
ACS pharmacology & translational science
|March 20, 2025
概括
这项研究表明,与标记Technetium-99m (99mTc) 的版本相比,印-111 (111In) 标记的Affibody分子在癌症中提供了B7-H3 (CD276) 表达的优越成像. 111In-SYNT179-DOTA追踪器显示瘤吸收和对比度显著提高,这使得它成为向癌症治疗选择的前景.
科学领域:
- 核医学是一种核医学.
- 在瘤学瘤学.
- 放射性药物化学 放射性药物化学
背景情况:
- B7-H3 (CD276) 在各种癌症中过度表达,使其成为重要的治疗点.
- 使用像Affibody分子这样的工程脚手架蛋白质进行放射性核素分子成像对于识别可能受益于B7-H3向治疗的患者至关重要.
- 以前的研究表明,使用99mTc标记的探针进行B7-H3成像的可行性.
研究的目的:
- 评估基于111In的残留标签是否与非残留标签相比,提高了B7-H3表达的成像对比度.
- 为了比较111In标记的亲体分子 (SYNT179和AC12-GGGC) 与99mTc标记的对应分子的性能.
主要方法:
- 通过使用maleimide-DOTA化剂,SYNT179和AC12-GGGC亲体分子被特定地标记为111In.
- 用B7-H3-表达细胞评估了111In和99mTc标记的结合物的结合亲和力.
- 活体成像研究在携带B7-H3表达异位移植的小鼠中进行,以测量瘤吸收和生物分布.
主要成果:
- 标记为111In的亲体分子的结合亲缘关系比标记为99mTc的变体更高.
- 标记为111In的蛋白质 ([111In]In-SYNT179-DOTA和[111In]In-AC12-DOTA) 的瘤吸收明显高 (p <0.05) 于标记为99mTc的对应物.
- [111]In-SYNT179-DOTA的瘤与血液的比率为31.1±2.9,是[99mTc]Tc-SYNT179的两倍,是[99mTc]Tc-AC12-GGGC的七倍. 在111In标记的探针中,肝胆道分泌量较低.
结论:
- 与非残留99mTc标签相比,残留111In标签显著改善了B7-H3表达的成像对比度.
- [111In]In-SYNT179-DOTA表现出卓越的性能,显示出高瘤吸收率和有利的生物分布.
- [111]In-SYNT179-DOTA被确定为在向癌症治疗的背景下可视化B7-H3表达的最有前途的放射追踪器.
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