[99mTc]Tc-PentixaTec:开发,广泛的临床前评估,以及人类第一次体验
Matthias Konrad1, Andreas Rinscheid2, Georgine Wienand3
1Chair for Pharmaceutical Radiochemistry, Faculties of Chemistry and Medicine, Technische Universität München, 85748, Garching, Germany.
European journal of nuclear medicine and molecular imaging
|August 19, 2023
概括
研究人员开发了[99mTc]Tc-PentixaTec,这是一种针对CXCR4的新型SPECT成像剂. 这种药物表现出高亲和力,高效的内化和有利的剂量测量,使其在血液恶性瘤的临床使用中具有前景.
科学领域:
- 核医学就是核医学.
- 放射化学 放射化学是指辐射化学.
- 在瘤学瘤学.
背景情况:
- 在血液性恶性瘤中,CXCR4表达非常重要.
- 对CXCR4的非侵入性成像具有临床价值.
- 现有的PET剂,如[68Ga]Ga-PentixaFor是有效的,但成本高昂.
研究的目的:
- 开发和评估用于CXCR4的SPECT成像的新型99mTc标记循环五.
- 优化标签策略和链接器结构,以提高亲和度和准度.
- 为了评估领先候选人的临床前和临床早期表现, [99mTc]Tc-PentixaTec.
主要方法:
- 合成了六种mas3-结合的CPCR4类型,具有不同的链接器.
- 使用mas3,HYNIC和N4策略使用99mTc进行放射性标记.
- 使用癌细胞系的体外结合和内化研究.
- 在小鼠体内生物分布和SPECT/CT成像.
- 在患有血液性恶性瘤的患者中,早期人类SPECT/平面成像和剂量测量.
主要成果:
- N4-L6-CPCR4显示出最高的亲和力 (0.6 ± 0.1 nM) 和高效的内部化 (97%在2小时).
- [99mTc]Tc-N4-L6-CPCR4 ([99mTc]Tc-PentixaTec) 显示了高瘤吸收率 (8.6 ± 1.3% iD/g 在下午1小时. ) 的情况.
- 人类研究证实了良好的耐受性,有利的生物分布,剂量测量 (2.1-3.4 mSv) 和优秀的瘤与背景比率.
结论:
- [99mTc]Tc-PentixaTec是一种非常有前途的CXCR4向的SPECT剂.
- 对链接器和标签策略的优化产生了一种优异的放射性追踪器.
- 该药物具有出色的临床前和临床特征,用于诊断和监测表达CXCR4的恶性瘤.
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