title: Development of a (99m)Tc-labeled lactam bridge-cyclized alpha-MSH derivative peptide as a possible single photon imaging agent for melanoma tumors.
abstract: OBJECTIVE
  Melanocortin-1 (MC1) receptor is an attractive melanoma-specific target which has been used for melanoma imaging and therapy. In this work, a new lactam bridge α-MSH analog was labeled with (99m)Tc via HYNIC and EDDA/tricine as coligands including gamma aminobutyric acid (GABA) as a three carbon chain spacer between HYNIC and the N-terminus of the cyclic peptide. Also, stability in human serum, receptor bound internalization, in vivo tumor uptake, and tissue biodistribution were thoroughly investigated.
  
  
  METHODS
  HYNIC-GABA-Nle-CycMSHhept was synthesized using a standard Fmoc strategy. Labeling was performed at 95 °C and analysis involved instant thin layer chromatography and high performance liquid chromatography methods. The receptor bound internalization rate was studied in MC1 receptor expressing B16/F10 cells. Biodistribution of radiopeptide was studied in nude mice bearing B16/F10 tumor.
  
  
  RESULTS
  Labeling yield of >98 % (n = 3) was obtained corresponding to a specific activity of 81 MBq/nmol. Peptide conjugate showed efficient stability in the presence of human serum. The radioligand showed specific internalization into B16/F10 cells (12.45 ± 1.1 % at 4 h). In biodistribution studies, a receptor-specific uptake was observed in MC1 receptor-positive organs so that after 2 h the uptake in mouse tumor was 5.10 ± 0.08 % ID/g, while low accumulation in the kidney uptake was observed (4.58 ± 0.68 % ID/g at 2 h after injection).
  
  
  CONCLUSIONS
  The obtained results show that the presented new designed labeled peptide conjugate may be a suitable candidate for diagnosis of malignant tumors.
authors.affiliation: Department of Radiopharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Danial
authors.initials: D
authors.lastname: Shamshirian
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), P.O.Box: 14395-836, Tehran, Iran. mgandomkar@aeoi.org.ir.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Erfani
authors.affiliation: Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Davood
authors.initials: D
authors.lastname: Beiki
authors.affiliation: Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Babak
authors.initials: B
authors.lastname: Fallahi
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), P.O.Box: 14395-836, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shafiei
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D004355:Drug Stability; D006834:Hydrazines / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D007769:Lactams / Q000737:chemistry*; D008545:Melanoma / Q000000981:diagnostic imaging*; D051379:Mice; D009539:Nicotinic Acids / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D017785:Photons; D011877:Radionuclide Imaging / Q000379:methods*; D013667:Technetium; D014018:Tissue Distribution; D000521:alpha-MSH / Q000737:chemistry*; D005680:gamma-Aminobutyric Acid / Q000737:chemistry
chemical_list: C120392:6-hydrazinopyridine-3-carboxylic acid; D006834:Hydrazines; D007769:Lactams; D009539:Nicotinic Acids; D010456:Peptides, Cyclic; D005680:gamma-Aminobutyric Acid; D000521:alpha-MSH; D013667:Technetium
keywords: 99mTc; B16/F10 cells; Tumor imaging; α-MSH