Li W P, Anderson C J
Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Q J Nucl Med. 2003 Sep;47(3):201-8.
metastatic Matrix metalloproteinases (MMPs) are zinc-dependent secreted or transmembrane enzymes constituting a family of over 21 proteolytic members that are capable of selectively digesting a wide spectrum of both extracellular matrix (ECM) and nonmatrix proteins. MMPs play a critical role in tumor growth, angiogenesis, and metastatic processes. MMP inhibitors (MMPIs) have been extensively investigated as anti-tumor drugs, although the clinical trials thus far have been disappointing. In order to better understand the role of MMPs in cancer growth and metastasis, as well as improve the therapeutic efficacy of MMPIs, there is a need to develop new procedures to assess and/or monitor MMP activity in vivo. In addition to determining whether MMPs are present in tumors, it would be desirable to have an imaging agent that better probes other processes associated with MMP overproduction, including angiogenesis and the establishment of the growth of metastatic lesions in distant organ sites. In this paper we review the studies relating to the recent development of in vivo imaging of MMP expression. One of the purposes of this review is to discuss the current status of imaging MMP expression, which includes the types of tracers being developed and the types of imaging modalities available. Although imaging MMP expression is a relatively new area of research, the progress thus far is highly promising.
转移性基质金属蛋白酶(MMPs)是一类依赖锌的分泌型或跨膜酶,由超过21种蛋白水解成员组成,能够选择性地消化多种细胞外基质(ECM)和非基质蛋白。MMPs在肿瘤生长、血管生成和转移过程中起着关键作用。MMP抑制剂(MMPIs)作为抗肿瘤药物已得到广泛研究,尽管迄今为止的临床试验结果令人失望。为了更好地理解MMPs在癌症生长和转移中的作用,以及提高MMPIs的治疗效果,需要开发新的程序来评估和/或监测体内MMP活性。除了确定肿瘤中是否存在MMPs外,还需要一种成像剂,能够更好地探测与MMP过度产生相关的其他过程,包括血管生成和远处器官部位转移病灶生长的建立。在本文中,我们综述了与MMP表达的体内成像最新进展相关的研究。本综述的目的之一是讨论成像MMP表达的现状,包括正在开发的示踪剂类型和可用的成像方式类型。尽管成像MMP表达是一个相对较新 的研究领域,但迄今为止取得的进展非常有前景。