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

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[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.