title: Alpha-melanocyte-stimulating hormone peptide analogs labeled with technetium-99m and indium-111 for malignant melanoma targeting.
abstract: BACKGROUND
  Previous studies have shown that the compact structure of a rhenium-cyclized alpha--melanocyte-stimulating hormone peptide analog, [Cys3410,D-Phe7]alpha-MSH(3--13), or Re-CCMSH, significantly enhanced its in vivo tumor uptake and retention. In this study, the metal chelate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was coupled to the N-terminus of Re-CCMSH in order to develop a melanoma-targeting peptide that could be labeled with a wider variety of imaging and therapeutic radionuclides.
  
  
  METHODS
  Biodistribution properties of indium-111 ((111)In)--labeled DOTA-Re-CCMSH were compared with the non-DOTA-containing technetium-99m ((99m)Tc)--CCMSH in murine melanoma--bearing C57 mice to determine the effects of DOTA on tumor uptake and whole-body clearance. The tumor targeting capacity and clearance kinetics of (111)In-DOTA-Re-CCMSH were also compared with other related cyclic and linear (111)In-labeled DOTA-alpha-MSH complexes.
  
  
  RESULTS
  The in vivo distribution data showed that the conjugation of DOTA to Re-CCMSH did not reduce its initial tumor uptake kinetics but did enhance its tumor retention and renal clearance properties. The tumor uptake of (111)In-DOTA-Re-CCMSH was significantly higher than the other (111)In-DOTA--coupled cyclic or linear alpha-MSH analogs used in this study. Moreover, (111)In-DOTA-Re-CCMSH displayed lower radioactivity accumulation in normal tissues of interest than its non-Re-cyclized counterpart, (111)In-DOTA-CCMSH; the disulfide bond--cyclized (111)In-DOTA-CMSH; or the linear (111)In-DOTA-NDP.
  
  
  CONCLUSIONS
  Peptide cyclization via rhenium coordination significantly enhanced the tumor targeting and renal clearance properties of DOTA-Re-CCMSH, making it an excellent candidate for melanoma radiodetection and radiotherapy.
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, Missouri, USA. jchen@bru.bracco.com
authors.forename: JianQing
authors.initials: J
authors.lastname: Chen
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
authors.forename: Yubin
authors.initials: Y
authors.lastname: Miao
authors.forename: Silvia S
authors.initials: SS
authors.lastname: Jurisson
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Quinn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D007204:Indium / Q000737:chemistry / Q000493:pharmacokinetics*; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000737:chemistry / Q000493:pharmacokinetics; D011878:Radiotherapy; D013667:Technetium / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D000521:alpha-MSH / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000970:Antineoplastic Agents; D010446:Peptide Fragments; D007204:Indium; D000521:alpha-MSH; D013667:Technetium