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.
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.
Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-712, Republic of Korea.
Eun-Mi
EM
Kim
Min-Hee
MH
Joung
Chang-Moon
CM
Lee
Hwan-Jeong
HJ
Jeong
Seok Tae
ST
Lim
Myung-Hee
MH
Sohn
Dong Wook
DW
Kim
D006801:Humans; D009369:Neoplasms / Q000175:diagnosis*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D013667:Technetium / Q000737:chemistry*; D014230:Triazoles / Q000737:chemistry*
D014230:Triazoles; D013667:Technetium; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases