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设计和临床前评估68Ga标记的宏环PET探针向结肠直肠癌中的转激素受体1

Yuchun Zhu¹, Lian Wang², Qingyan Tang³

¹Department of Nuclear Medicine, Kunshan First People's Hospital, Kunshan 215399, China.

|January 1, 2026

概括

一个新的加-68标记的探头,Ga-NOTA-TR01,在结肠直肠癌中有效地对转移素受体1 (TfR1) 进行图像. 这提供了一个非侵入性的工具,用于精确的诊断和治疗指导在CRC患者.

科学领域:

核医学是一种核医学.
在瘤学瘤学.
分子成像学分子成像学

背景情况:

转激素受体1 (TfR1/CD71) 在结直肠癌 (CRC) 中过度表达,与不良结果相关.
目前用于评估TfR1的免疫组织化学 (IHC) 方法受到空间异质性的限制.
需要使用非侵入性成像技术,根据TfR1表达,精确诊断和分层CRC患者.

研究的目的:

开发和评估Ga-NOTA-TR01,一种用于TfR1.1的新型正子发射断层扫描 (PET) 成像剂.
评估探针在结直肠癌中对TfR1进行非侵入性分子成像的潜力.
确定Ga-NOTA-TR01是否可以帮助精确诊断和治疗CRC的分层.

主要方法:

合成和放射性标记的宏环前体NOTA-TR01与68Ga.
对Ga-NOTA-TR01.68的放射化学纯度,摩尔活性,稳定性和脂友性进行评估.
在体外研究包括结合亲和力 (SPR),流细胞计和细胞测试.
在体内使用microPET/CT成像和生物分布研究在携带瘤的小鼠的评估,具有IHC验证.

主要成果:

合成的Ga-NOTA-TR01具有高放射性化学纯度 (>99%),高分子活性 (>20 GBq/μmol) 和优异的稳定性 (>98%在24小时).
探针表现出强大的结合亲和力 (K _D = 2.23 × 10^{- exto8} M) 和对TfR1表达细胞的特定结合.
微PET/CT成像显示TfR1-高瘤的特定瘤吸收,与TfR1-低瘤相比,瘤与背景比率显著更高.
阻断研究和生物分布证实了Ga-NOTA-TR01对TfR1在体内的特异性.

结论:

Ga-NOTA-TR01是一种高亲和度,代谢稳定的PET成像剂,用于TfR1.
该探测器在结直肠癌模型中专门可视化TfR1表达in vivo.
这种新型药物对TfR1-阳性CRC的非侵入性患者分层,治疗监测和预后评估具有前景.

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