Novel Matrix Metalloproteinase 12 selective radiotracers for vascular molecular imaging.
Novel Matrix Metalloproteinase 12 selective radiotracers for vascular molecular imaging.
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DOI：
10.1021/acs.jmedchem.9b01186
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发表时间：
2019-10
影响因子：
7.3
通讯作者：
Jakub Toczek;Thomas Bordenave;K. Gona;Hye-Yeong Kim;F. Beau;D. Georgiadis;Isabelle Correia;Y. Ye;Mahmoud Razavian;Jaejoon Jung;O. Lequin;V. Dive;M. Sadeghi;L. Devel
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文献类型：
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作者：
Jakub Toczek;Thomas Bordenave;K. Gona;Hye-Yeong Kim;F. Beau;D. Georgiadis;Isabelle Correia;Y. Ye;Mahmoud Razavian;Jaejoon Jung;O. Lequin;V. Dive;M. Sadeghi;L. Devel
基质金属蛋白酶-12（MMP-12）在包括腹主动脉瘤（AAA）在内的几种炎性疾病中高度上调。在这里，我们报告了四种新的99 mTc标记的放射性示踪剂来自一个高度选择性的竞争性MMP-12抑制剂。这些示踪剂以其99 gTc形式在体外对一组人金属蛋白酶进行评估，并显示出对MMP-12的高亲和力和选择性。它们用99 mTc的放射性标记在缓冲液和小鼠血液中均显示出有效和稳定。示踪剂在生物分布和血液清除率方面存在重大差异。基于其体内性能，选择[99 mTc]-1用于在MMP-12基因表达上调的鼠AAA中进行评价。注射后2小时的腹主动脉放射自显影显示相对于邻近主动脉，AAA中的[99 mTc]-1摄取较高。通过体内竞争证明了示踪剂摄取特异性。这项研究为进一步评价[99 mTc]-1对AAA和其他MMP-12相关疾病的成像铺平了道路。
Matrix metalloproteinase-12 (MMP-12) is highly upregulated in several inflammatory diseases, including abdominal aortic aneurysm (AAA). Here we report four novel 99mTc-labeled radiotracers derived from a highly selective competitive MMP-12 inhibitor. These tracers in their 99gTc version were assessed in vitro on a set of human metalloproteases and displayed high affinity and selectivity toward MMP-12. Their radiolabeling with 99mTc was shown to be efficient and stable in both buffer and mouse blood. The tracers showed major differences in their biodistribution and blood clearance. Based on its in vivo performance, [99mTc]-1 was selected for evaluation in murine AAA, where MMP-12 gene expression is upregulated. Autoradiography of aortae at two hours post-injection revealed high uptake of [99mTc]-1 in AAA relative to adjacent aorta. Tracer uptake specificity was demonstrated through in vivo competition. This study paves the way for further evaluation of [99mTc]-1 for imaging AAA and other MMP-12-associated diseases.