Abstract
1093
Objectives We reported a dual receptor-targeting α-melanocyte stimulating hormone (α-MSH) hybrid peptide {99mTc-RGD-Lys-(Arg11)CCMSH} for human melanoma imaging in our previous work. Despite its success in M21 human melanoma imaging, it is desirable to reduce its high renal uptake (67.1 ± 16.5% ID/g at 2 h post-injection). The purpose of this study was to examine the effect of hydrocarbon (βAla and Ahx) and polyethylene glycol (PEG) linkers on tumor and renal uptake of dual receptor-targeting 99mTc-labeled Arg-Gly-Asp-conjugated α-MSH hybrid peptides.
Methods The RGD motif {Arg-Gly-Asp-DTyr-Asp} was coupled to [Cys3,4,10, D-Phe7, Arg11]α-MSH3-13 via the βAla, Ahx, or PEG2 linker to generate RGD-linker-(Arg11)CCMSH peptides. The biodistribution results of 99mTc-RGD-linker-(Arg11)CCMSH peptides were examined in M21 human melanoma-xenografted nude mice.
Results The substitution of Lys linker with hydrocarbon and PEG2 linkers significantly decreased the renal uptake of 99mTc-RGD-linker-(Arg11)CCMSH peptides by 67-82% at 2 h post-injection as compared to 99mTc-RGD-Lys-(Arg11)CCMSH. Among these three 99mTc-peptides, 99mTc-RGD-βAla-(Arg11)CCMSH displayed the highest tumor uptake (2.37 ± 0.07% ID/g) and the lowest renal uptake (12.4 ± 0.1% ID/g) at 2 h post-injection.
Conclusions The favorable effect of hydrocarbon and PEG2 linkers in reducing the renal uptake provided a new insight into the design of novel dual receptor-targeting radiolabeled peptides.