Radio-labeling Of T7Peptide With^99mTc And Its Biodistribution Study Used For Tumor Angiogenesis Of Integrin αvβ3Receptor Imaging Agents

Tumor’s occurrence and metastasis rely on angiogenesis. The integrin αvβ3receptor had a high expression level on the surface of tumor angiogenesis endothelial cells and parts of the tumor cells. It had been confirmed that the integrin αvβ3receptor plays an important role in angiogenesis, growth and metastasis. Tumor’s molecular changes has always been earlier than its organizational and functional changes. So it can be a very promising target receptor for tumor’s early imaging, and can provide an effective approach for the assessment of the efficacy of anti-angiogenesis drugs.T7consists of25peptides which derived from type Ⅳ collagen. The sequence of T7is Thr-Met-Pro-Phe-Leu-Phe-Cys-Asn-Val-Asn-Asp-Val-Cys-Asn-Phe-Ala-Ser-Arg-Asn-Asp-Tyr-Ser-Tyr-Trp-Leu (TMPFLFCNVNDVCNFASRNDYSYWL). With its low molecular weight (2.75kD, M=2800), low immunogenicity, better lipotropy, specific binding sites and activity, it can specificly bind to the integrin αvβ3receptor in an RGD-independent way and inhibit tumor angiogenesis. T7is a very promising tumor targeting probe.The aim of the present study was to explore the feasibility of T7peptide used as the targeting imaging agents for integrin αvβ3receptor. At first, we detected the integrin αvβ3receptor’s expression level on the surface of human microvascular endothelial cells HMEC-1, a variety of tumor cells, like the human glioma cells U251, human esophageal cancer cells EC109, human larynx cancer cells Hep2, human liver cancer cells HepG2, human lung cancer cells, such as NCI-H157, NCI-H460and A549, human breast cancer cells, such as the MCF-7and MDA-MB-231, human prostate cancer cells PC3, by Flow Cytometry technique (FCM). Selected the tumor cells which had the highest expression level of integrin avP3receptor, and constructed its tumor-bearing nude mice model. The T7peptide was labeled with carbonyl technetium, and injected into the nude mice model by the intravenous injection (iv). Detecting the biodistribution of99mTc-T7in the nude mice model, and calculated the tumor/non-tumor tissues (T/NT)’s radioactive ratio. Observe that whether there is an assemble at the tumor sites of the99mTc-T7, and observe99mTc-T7’s pharmacokinetic properties in vivo of nude mice model.By the FCM detecting, we found that the human non-small cell lung cancer cells NCI-H157had a high expression level of integrin αvβ3receptor.99mTc-labeled T7showed good stability in vitro and high radiochemical purity over90%.99mTc-T7showed a high gatherd at the tumor sites in the NSCLC model. The tumor/muscle’s radioactive ratio increased with the time expansion, and can be up to5(T/NT). It’s better to get the results at4h to8h. The results showed that99mTc-T7maybe a promising imaging agents for the targeting imaging of integrin avP3receptor. It can be used at the tumor’s early imaging, and provide an effective approach for the efficacy assessment of anti-angiogenesis drugs.