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

Nucl Med Biol. 2010 Nov;37(8):873-83. doi: 10.1016/j.nucmedbio.2010.05.006. Epub 2010 Jul 24.


Introduction: The purpose of this study was to examine whether (99m)Tc-labeled Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone (α-MSH) hybrid peptide targeting both melanocortin-1 (MC1) and α(v)β(3) integrin receptors was superior in melanoma targeting to (99m)Tc-labeled α-MSH or RGD peptide targeting only the MC1 or α(v)β(3) integrin receptor.

Methods: RGD-Lys-(Arg(11))CCMSH, RAD-Lys-(Arg(11))CCMSH and RGD-Lys-(Arg(11))CCMSHscramble were designed to target both MC1 and α(v)β(3) integrin receptors, MC1 receptor only and α(v)β(3) integrin receptor only, respectively. The MC1 or α(v)β(3) integrin receptor binding affinities of three peptides were determined in M21 human melanoma cells. The melanoma targeting properties of (99m)Tc-labeled RGD-Lys-(Arg(11))CCMSH, RAD-Lys-(Arg(11))CCMSH and RGD-Lys-(Arg(11))CCMSHscramble were determined in M21 human melanoma-xenografted nude mice. Meanwhile, the melanoma uptake of (99m)Tc-RGD-Lys-(Arg(11))CCMSH was blocked with various non-radiolabeled peptides in M21 melanoma xenografts.

Results: RGD-Lys-(Arg(11))CCMSH displayed 2.0 and 403 nM binding affinities to both MC1 and α(v)β(3) integrin receptors, whereas RAD-Lys-(Arg(11))CCMSH or RGD-Lys-(Arg(11))CCMSHscramble lost their α(v)β(3) integrin receptor binding affinity by greater than 248-fold or MC1 receptor binding affinity by more than 100-fold, respectively. The melanoma uptake of (99m)Tc-RGD-Lys-(Arg(11))CCMSH was 2.49 and 2.24 times (P < .05) the melanoma uptakes of (99m)Tc-RAD-Lys-(Arg(11))CCMSH and (99m)Tc-RGD-Lys-(Arg(11))CCMSHscramble at 2 h post-injection, respectively. Either RGD or (Arg(11))CCMSH peptide co-injection could block 42% and 57% of the tumor uptake of (99m)Tc-RGD-Lys-(Arg(11))CCMSH, whereas the coinjection of RGD+(Arg(11))CCMSH peptide mixture could block 66% of the tumor uptake of (99m)Tc-RGD-Lys-(Arg(11))CCMSH.

Conclusions: Targeting both MC1 and α(v)β(3) integrin receptors enhanced the melanoma uptake of (99m)Tc-RGD-Lys-(Arg(11))CCMSH in M21 human melanoma xenografts. Flank M21 human melanoma tumors were clearly visualized by single photon emission computed tomography/computed tomographic imaging using (99m)Tc-RGD-Lys-(Arg(11))CCMSH as an imaging probe, highlighting its potential use as a dual-receptor-targeting imaging probe for human melanoma detection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic
  • Drug Design
  • Feasibility Studies
  • Humans
  • Imaging, Three-Dimensional
  • Integrin alphaVbeta3 / metabolism
  • Melanoma / diagnostic imaging*
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Mice
  • Molecular Imaging / methods*
  • Oligopeptides / chemistry*
  • Oligopeptides / metabolism*
  • Oligopeptides / pharmacokinetics
  • Organotechnetium Compounds*
  • Receptor, Melanocortin, Type 1 / metabolism
  • Sugar Acids / chemistry
  • Tomography, Emission-Computed, Single-Photon
  • Tomography, X-Ray Computed
  • alpha-MSH / metabolism*


  • Integrin alphaVbeta3
  • Oligopeptides
  • Organotechnetium Compounds
  • Receptor, Melanocortin, Type 1
  • Sugar Acids
  • alpha-MSH
  • arginyl-glycyl-aspartic acid
  • alpha-glucoheptonic acid