title: Dual receptor-targeting ⁹⁹mTc-labeled Arg-Gly-Asp-conjugated Alpha-Melanocyte stimulating hormone hybrid peptides for human melanoma imaging.
abstract: BACKGROUND
  The 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 (99m)Tc-labeled Arg-Gly-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) hybrid peptides.
  
  
  METHODS
  The RGD motif {Arg-Gly-Asp-DTyr-Asp} was coupled to [Cys(3,4,10), D-Phe(7), Arg(11)]α-MSH₃₋₁₃ via the Aoc or PEG₂ linker to generate RGD-Aoc-(Arg(11))CCMSH and RGD-PEG-(Arg(11))CCMSH. The biodistribution results of (99m)Tc-RGD-Aoc-(Arg(11))CCMSH and (99m)Tc-RGD-PEG₂-(Arg(11))CCMSH were examined in M21 human melanoma-xenografted nude mice.
  
  
  RESULTS
  The substitution of Lys linker with Aoc and PEG₂ linker significantly reduced the renal uptake of (99m)Tc-RGD-Aoc-(Arg(11))CCMSH and (99m)Tc-RGD-PEG₂-(Arg(11))CCMSH by 58% and 63% at 2h post-injection. The renal uptake of (99m)Tc-RGD-Aoc-(Arg(11))CCMSH and (99m)Tc-RGD-PEG₂-(Arg(11))CCMSH was 27.93 ± 3.98 and 22.01 ± 9.89% ID/g at 2 h post-injection. (99m)Tc-RGD-Aoc-(Arg(11))CCMSH displayed higher tumor uptake than (99m)Tc-RGD-PEG₂-(Arg(11))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 (99m)Tc-RGD-Aoc-(Arg(11))CCMSH as an imaging probe.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USA.
authors.forename: Jingli
authors.initials: J
authors.lastname: Xu
authors.affiliation: College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USA.
authors.forename: Jianquan
authors.initials: J
authors.lastname: Yang
authors.affiliation: College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USA; Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131, USA; Department of Dermatology, University of New Mexico, Albuquerque, NM 87131, USA. Electronic address: ymiao@salud.unm.edu.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Miao
mesh_terms: D000818:Animals; D002210:Caprylates / Q000737:chemistry; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D003952:Diagnostic Imaging / Q000379:methods*; D006801:Humans; D007553:Isotope Labeling; D008546:Melanoma, Experimental / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry; D013667:Technetium; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D000521:alpha-MSH / Q000378:metabolism*
chemical_list: D002210:Caprylates; D009842:Oligopeptides; D011092:Polyethylene Glycols; D000521:alpha-MSH; D013667:Technetium; C047981:arginyl-glycyl-aspartic acid; C031492:octanoic acid
keywords: Alpha-melanocyte stimulating hormone hybrid peptide; Arg-Gly-Asp-conjugated; Dual receptor-targeting human melanoma imaging