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.
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