Structural modification on the Lys linker enhanced tumor to kidney uptake ratios of 99mTc-labeled RGD-conjugated α-MSH hybrid peptides.

The purpose of this study was to examine whether the structural modification on the positively charged Lys linker could reduce the kidney uptake of 99mTc-labeled Arg-Gly-Asp (RGD)-conjugated α-melanocyte stimulating hormone (α-MSH) hybrid peptides. The RGD motif {cyclic(Arg-Gly-Asp-d-Tyr-Asp)} was coupled to [Cys3,4,10, d-Phe7, Arg11]α-MSH3–13 {(Arg11)CCMSH} through a neutral glycine linker to eliminate the positively charged amino side chain of the Lys linker or without a linker to delete the Lys linker. The receptor binding affinity of RGD-Gly-(Arg11)CCMSH and RGD-(Arg11)CCMSH was determined in B16/F1 melanoma cells. The melanoma targeting and imaging properties of 99mTc-RGD-Gly-(Arg11)CCMSH and 99mTc-RGD-(Arg11)CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The structural modification on the Lys linker retained a low nanomolar receptor binding affinity of RGD-Gly-(Arg11)CCMSH and RGD-(Arg11)CCMSH (1.5 and 1.0 nM, respectively). The structural modification on the Lys linker dramatically decr...