Synthesis of Tc-99m labeled 1,2,3-triazole-4-yl c-met binding peptide as a potential c-met receptor kinase positive tumor imaging agent

Abstract

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 99mTc labeled cMBP derivatives ([99mTc(CO)3]12, [99mTc(CO)3]13, and [99mTc(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 (0.13μM, 0.06μM, and 0.16μM, 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 99mTc labeled cMBP derivatives ([99mTc(CO)3]12–14) to c-Met receptor positive U87MG cells.