In vivo molecular target assessment of matrix metalloproteinase inhibition
In vivo molecular target assessment of matrix metalloproteinase inhibition
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DOI：
10.1038/89126
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发表时间：
2001-06-01
期刊：
影响因子：
82.9
通讯作者：
Weissleder, R
中科院分区：
文献类型：
--
作者：
Bremer, C;Tung, CH;Weissleder, R
许多不同的基质金属蛋白酶（MMP）抑制剂已被开发为细胞生长抑制剂和抗血管生成剂，目前正在进行临床试验。评估此类药物功效的一个主要障碍是无法在体内直接和非侵入性地感测或成像抗蛋白酶活性。我们在这里表明，新的，生物相容性的近红外荧光MMP基板可用作可激活的报告探针，在裸鼠的完整肿瘤中检测MMP活性。此外，我们第一次表明，MMP抑制的效果可以直接使用这种方法在使用有效的MMP抑制剂普利诺司他（AC 3340）治疗开始后数小时内成像。开发的探针，连同新的近红外荧光成像技术，将能够详细分析一些蛋白酶的关键推进临床蛋白酶抑制剂的治疗用途。
A number of different matrix metalloproteinase (MMP) inhibitors have been developed as cytostatic and anti-angiogenic agents and are currently in clinical testing. One major hurdle in assessing the efficacy of such drugs has been the inability to sense or image anti-proteinase activity directly and non-invasively in vivo. We show here that novel, biocompatible near-infrared fluorogenic MMP substrates can be used as activatable reporter probes to sense MMP activity in intact tumors in nude mice. Moreover, we show for the first time that the effect of MMP inhibition can be directly imaged using this approach within hours after initiation of treatment using the potent MMP inhibitor, prinomastat (AC3340). The developed probes, together with novel near-infrared fluorescence imaging technology will enable the detailed analysis of a number of proteinases critical for advancing the therapeutic use of clinical proteinase inhibitors.