Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.
Curr Pharm Des. 2013;19(25):4647-72. doi: 10.2174/1381612811319250011.
Dysregulation of matrix metalloproteinase (MMP) activity can lead to a wide range of disease states such as atherosclerosis, inflammation or cancer. The ability to image MMP activity non-invasively in vivo, by radiolabelled synthetic inhibitors, would allow the characterization of atherosclerotic plaques, inflammatory lesions or tumors. Here we present an overview of radiolabelled MMP inhibitors (MMPIs) and MMP peptides for positron emission tomography (PET) and single photon emission computed tomography (SPECT) for the detection of proteolytic activity of MMPs. So far, most studies are at a preliminary stage; however, some hydroxamate-based tracers such as the peptidomimetics [¹¹¹In]-DTPA-RP782, [99mTc]-(HYNIC-RP805)(tricine)(TPPTS), or Marimastat-ArB[¹⁸F]F₃ and the picolyl- benzenesulfonamide [¹²³I]I-HO-CGS 27023A identified specifically the enzymatic action of MMPs in animal models of various pathologies. The development of new compounds that may lead to novel tracers (e.g. modification of zinc-binding group, variation of substituents attached to the S1', S2' and S3' pockets of the MMP inhibitors) and the use of antibodies and cell penetrating peptides are also discussed. In general, preclinical studies with atherosclerosis models proved to be more successful than those with oncological models.
基质金属蛋白酶（MMP）活性的失调可导致多种疾病状态，如动脉粥样硬化、炎症或癌症。通过放射性标记的合成抑制剂非侵入性地体内成像 MMP 活性的能力将允许对动脉粥样硬化斑块、炎症病变或肿瘤进行特征描述。在这里，我们概述了用于正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）的放射性标记 MMP 抑制剂（MMPI）和 MMP 肽，以检测 MMP 的蛋白水解活性。到目前为止，大多数研究都处于初步阶段；然而，一些基于羟肟酸的示踪剂，如肽模拟物 [¹¹¹In]-DTPA-RP782、[99mTc]-(HYNIC-RP805)(tricine)(TPPTS)、或 Marimastat-ArB[¹⁸F]F₃ 和吡啶基-苯磺酰胺 [¹²³I]I-HO-CGS 27023A，在各种病理动物模型中特异性地鉴定了 MMP 的酶促作用。还讨论了开发可能导致新型示踪剂的新化合物（例如锌结合基团的修饰、附着在 MMP 抑制剂的 S1'、S2'和 S3'口袋上的取代基的变化）以及使用抗体和细胞穿透肽。一般来说，与肿瘤模型相比，在动脉粥样硬化模型中的临床前研究更成功。
