Dual receptor-targeting 99mTc-labeled Arg-Gly-Asp-conjugated Alpha-Melanocyte stimulating hormone hybrid peptides for human melanoma imaging

IntroductionThe aim of this study was to examine whether the substitution of the Lys linker with the aminooctanoic acid (Aoc) and polyethylene glycol (PEG) linker could substantially decrease the non-specific renal uptake of 99mTc-labeled Arg-Gly-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) hybrid peptides.MethodsThe RGD motif {Arg-Gly-Asp-DTyr-Asp} was coupled to [Cys3,4,10, D-Phe7, Arg11]α-MSH3–13 via the Aoc or PEG2 linker to generate RGD-Aoc-(Arg11)CCMSH and RGD-PEG-(Arg11)CCMSH. The biodistribution results of 99mTc-RGD-Aoc-(Arg11)CCMSH and 99mTc-RGD-PEG2-(Arg11)CCMSH were examined in M21 human melanoma-xenografted nude mice.ResultsThe substitution of Lys linker with Aoc and PEG2 linker significantly reduced the renal uptake of 99mTc-RGD-Aoc-(Arg11)CCMSH and 99mTc-RGD-PEG2-(Arg11)CCMSH by 58% and 63% at 2 h post-injection. The renal uptake of 99mTc-RGD-Aoc-(Arg11)CCMSH and 99mTc-RGD-PEG2-(Arg11)CCMSH was 27.93 ± 3.98 and 22.01 ± 9.89% ID/g at 2 h post-injection. 99mTc-RGD-Aoc-(Arg11)CCMSH displayed higher tumor uptake than 99mTc-RGD-PEG2-(Arg11)CCMSH (2.35 ± 0.12 vs. 1.71 ± 0.25% ID/g at 2 h post-injection). The M21 human melanoma lesions could be clearly visualized by SPECT/CT using 99mTc-RGD-Aoc-(Arg11)CCMSH as an imaging probe.ConclusionsThe favorable effect of Aoc and PEG2 linker in reducing the renal uptake provided a new insight into the design of novel dual receptor-targeting radiolabeled peptides.