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

[目的]肝细胞生长因子(HGF)的特异性受体c-Met作为治疗肿瘤和缺血性疾病的重要靶点，一直受到人们的关注。由于在细胞表面进行c-蛋氨酸成像可以为诊断肿瘤的恶性程度和决定治疗策略提供有用的信息，并在决定治疗药物在缺血性疾病中的有效给药部位提供有用的信息，本研究的目的是开发一种靶向c-蛋氨酸的分子显像剂。该探针的基本结构由肝细胞生长因子α链N末端的73个氨基酸多肽序列组成，含有肝素结合部位，我们使用^&lt；125&gt；I标记和^&lt；123&gt；用肝素柱法和表达c-Met的癌细胞体外实验证实标记的探针保留了肝素结合活性和c-Met结合活性。在c-Met表达癌细胞的异种移植模型中观察到标记探针的高度聚集，在心肌缺血模型中观察到c-Met表达增加的梗死区。由于该探针能够对肿瘤和缺血性疾病中c-Met的表达进行无创性成像，因此它似乎将有助于临床诊断和监测治疗，并将能够促进针对c-Met的药物和治疗方法的发展。

[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.