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

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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 (0.13 μM, 0.06 μM, and 0.16 μM, 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.

Graphical abstract

Tc-99m labeled 1,2,3-triazole-4-yl c-Met binding peptide (cMBP), as a potential c-Met receptor kinase positive tumor imaging agent, were prepared by solid phase peptide synthesis and the ‘click-to-chelate’ protocol.

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Acknowledgments

This work was supported by research funds of Chonbuk National University in 2010, Nuclear Research & Development Program of the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean government (MEST). (Grant code: 2009-0078422 to D.W.K) and the Conversing Research Center Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (Grant code: 2009-0081956)

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