Molecular targeting imaging of angiogenesis using hepatocyte growth as a probe in ischemia and tumor models.

[目的]c-Met是肝细胞生长因子（hepatocyte growth factor，HGF）的特异性受体，是肿瘤和缺血性疾病治疗的重要靶点。由于在细胞表面对c-Met进行成像可以为诊断肿瘤的恶性程度和决定肿瘤的治疗策略以及决定缺血性疾病中有效施用治疗剂的部位提供有用的信息，本研究的目的是开发一种靶向c-Met的分子显像剂，该探针的基本结构由73个氨基酸组成（HGF [11-83]）序列，该序列含有肝素结合位点，我们使用~（14）<125>I标记和~<123>（14）I标记的多肽对探针进行了评价。通过使用肝素柱法和表达c-Met的癌细胞，在体外证实了标记探针的肝素结合活性和c-Met结合活性的保留。在移植了表达c-Met的癌细胞的异种移植模型中观察到标记探针的高蓄积，在心肌缺血模型中，在被认为c-Met表达增加的梗死边界区域观察到标记探针的蓄积。由于该探针能够对肿瘤和缺血性疾病中的c-Met表达进行非侵入性成像，因此看起来它将有助于临床诊断和监测治疗，并且它将能够有助于促进靶向c-Met的药物和治疗方法的开发。

[Purpose]c-Met, the specific receptor for hepatocyte growth factor (HGF), has been attracting interest as an important target for the development of treatments for tumors and ischemic diseases. Since imaging c-Met at the cell surface may provide useful information for diagnosing the degree of malignancy and deciding on treatment policy in tumors, and in deciding on sites for effective administration of therapeutic agents in ischemic diseases, our aim in this study was to develop a molecular imaging agent that targeted c-Met.The basic structure of the probe consists of the 73-amino-acid polypeptide (HGF [11-83]) sequence of the α-chain N-terminal of HGF, which contains the heparin binding site, and we used ^<125>I-labeled and ^<123>I-labeled polypeptides to evaluate the probe.Retention of heparin-binding activity and c-Met-binding activity by the labeled probes was confirmed in vitro by using the heparin-column method and c-Met-expressing cancer cells. High accumulation of the labeled probes was observed in the xenograft model implanted with c-Met-expressing cancer cells, and accumulation was observed in the infarct boundary region, where c-Met expression is said to be increased, in the myocardial ischemia model.Because this probe enables non-invasive imaging of c-Met expression in tumors and ischemic diseases, it seems that it will be useful for clinical diagnosis and monitoring treatment, and that it will be able to contribute to promoting the development of drugs and methods of treatment that target c-Met.