Technetium-99m-labeled Arg-Gly-Asp-conjugated alpha-melanocyte stimulating hormone hybrid peptides for human melanoma imaging

IntroductionThe purpose of this study was to examine whether 99mTc-labeled Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone (α-MSH) hybrid peptide targeting both melanocortin-1 (MC1) and αvβ3 integrin receptors was superior in melanoma targeting to 99mTc-labeled α-MSH or RGD peptide targeting only the MC1 or αvβ3 integrin receptor.MethodsRGD-Lys-(Arg11)CCMSH, RAD-Lys-(Arg11)CCMSH and RGD-Lys-(Arg11)CCMSHscramble were designed to target both MC1 and αvβ3 integrin receptors, MC1 receptor only and αvβ3 integrin receptor only, respectively. The MC1 or αvβ3 integrin receptor binding affinities of three peptides were determined in M21 human melanoma cells. The melanoma targeting properties of 99mTc-labeled RGD-Lys-(Arg11)CCMSH, RAD-Lys-(Arg11)CCMSH and RGD-Lys-(Arg11)CCMSHscramble were determined in M21 human melanoma-xenografted nude mice. Meanwhile, the melanoma uptake of 99mTc-RGD-Lys-(Arg11)CCMSH was blocked with various non-radiolabeled peptides in M21 melanoma xenografts.ResultsRGD-Lys-(Arg11)CCMSH displayed 2.0 and 403 nM binding affinities to both MC1 and αvβ3 integrin receptors, whereas RAD-Lys-(Arg11)CCMSH or RGD-Lys-(Arg11)CCMSHscramble lost their αvβ3 integrin receptor binding affinity by greater than 248-fold or MC1 receptor binding affinity by more than 100-fold, respectively. The melanoma uptake of 99mTc-RGD-Lys-(Arg11)CCMSH was 2.49 and 2.24 times (P < .05) the melanoma uptakes of 99mTc-RAD-Lys-(Arg11)CCMSH and 99mTc-RGD-Lys-(Arg11)CCMSHscramble at 2 h post-injection, respectively. Either RGD or (Arg11)CCMSH peptide co-injection could block 42% and 57% of the tumor uptake of 99mTc-RGD-Lys-(Arg11)CCMSH, whereas the coinjection of RGD+(Arg11)CCMSH peptide mixture could block 66% of the tumor uptake of 99mTc-RGD-Lys-(Arg11)CCMSH.ConclusionsTargeting both MC1 and αvβ3 integrin receptors enhanced the melanoma uptake of 99mTc-RGD-Lys-(Arg11)CCMSH in M21 human melanoma xenografts. Flank M21 human melanoma tumors were clearly visualized by single photon emission computed tomography/computed tomographic imaging using 99mTc-RGD-Lys-(Arg11)CCMSH as an imaging probe, highlighting its potential use as a dual-receptor-targeting imaging probe for human melanoma detection.