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[摘要]：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 Tc-99m labeled cMBP derivatives ([Tc-99m(CO)(3)]12, [Tc-99m(CO)(3)]13, and [Tc-99m(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 mu M, 0.06 mu M, and 0.16 mu M, 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 Tc-99m labeled cMBP derivatives ([Tc-99m(CO)(3)]12-14) to c-Met receptor positive U87MG cells. (C) 2010 Elsevier Ltd. All rights reserved. |
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