Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-712, Republic of Korea.
Bioorg Med Chem Lett. 2010 Jul 15;20(14):4240-3. doi: 10.1016/j.bmcl.2010.05.036. Epub 2010 May 15.
The mesenchymal-epithelial transition factor (c-Met), which is related to tumor cell growth, angiogenesis and metastases, is known to be overexpressed in several tumor types. In this study, we synthesized technetium-99m labeled 1,2,3-triazole-4-yl c-Met binding peptide (cMBP) derivatives, prepared by solid phase peptide synthesis and the 'click-to-chelate' protocol for the introduction of tricarbonyl technetium-99m, as a potential c-Met receptor kinase positive tumor imaging agent, and evaluated their in vitro c-Met binding affinity, cellular uptake, and stability. The (99m)Tc labeled cMBP derivatives ([(99m)Tc(CO)(3)]12, [(99m)Tc(CO)(3)]13, and [(99m)Tc(CO)(3)]14) were prepared in 85-90% radiochemical yields. The cold surrogate cMBP derivatives, [Re(CO)(3)]12, [Re(CO)(3)]13, and [Re(CO)(3)]14, were shown to have high binding affinities (0.13 microM, 0.06 microM, and 0.16 microM, respectively) to a purified cMet/Fc chimeric recombinant protein. In addition, the in vitro cellular uptake and inhibition studies demonstrated the high specific binding of these (99m)Tc labeled cMBP derivatives ([(99m)Tc(CO)(3)]12-14) to c-Met receptor positive U87MG cells.
间质上皮转化因子（c-Met）与肿瘤细胞生长、血管生成和转移有关，已知在几种肿瘤类型中过度表达。在这项研究中，我们合成了放射性核素标记的 1,2,3-三唑-4-基 c-Met 结合肽（cMBP）衍生物，通过固相肽合成和“点击螯合”协议制备，用于引入三羰基锝-99m，作为一种潜在的 c-Met 受体激酶阳性肿瘤成像剂，并评估了它们的体外 c-Met 结合亲和力、细胞摄取率和稳定性。（99m）Tc 标记的 cMBP 衍生物([(99m)Tc(CO)(3)]12、[(99m)Tc(CO)(3)]13 和 [(99m)Tc(CO)(3)]14)以 85-90%的放射化学产率制备。冷替代 cMBP 衍生物[Re(CO)(3)]12、[Re(CO)(3)]13 和 [Re(CO)(3)]14 被证明对纯化的 cMet/Fc 嵌合重组蛋白具有高结合亲和力（分别为 0.13 μM、0.06 μM 和 0.16 μM）。此外，体外细胞摄取和抑制研究表明，这些（99m）Tc 标记的 cMBP 衍生物([(99m)Tc(CO)(3)]12-14)对 c-Met 受体阳性 U87MG 细胞具有高特异性结合。
