title: Therapeutic efficacy of a 188Re-labeled alpha-melanocyte-stimulating hormone peptide analog in murine and human melanoma-bearing mouse models.
abstract: The purpose of this study was to examine the therapeutic efficacy of (188)Re-(Arg(11))[Cys(3,4,10),d-Phe(7)]alpha-melanocyte-stimulating hormone(3-13) (CCMSH) in the B16/F1 murine melanoma- and TXM13 human melanoma-bearing mouse models.
  
  
  METHODS
  (Arg(11))CCMSH was synthesized and labeled with (188)Re to form (188)Re-(Arg(11))CCMSH. B16/F1 melanoma-bearing mice were administrated 7.4 MBq, 22.2 MBq, and 2 x 14.8 MBq of (188)Re-(Arg(11))CCMSH via the tail vein. TXM13 melanoma-bearing mice were separately injected with 22.2 MBq, 2 x 14.8 MBq, and 37.0 MBq of (188)Re-(Arg(11))CCMSH through the tail vein. Two groups of 10 mice bearing either B16/F1 or TXM13 tumors were injected with saline as untreated controls.
  
  
  RESULTS
  In contrast to the untreated control group, (188)Re-(Arg(11))CCMSH yielded rapid and lasting therapeutic effects in the treatment groups with either B16/F1 or TXM13 tumors. The tumor growth rate was reduced and the survival rate was prolonged in the treatment groups. Treatment with 2 x 14.8 MBq of (188)Re-(Arg(11))CCMSH significantly extended the mean life of B16/F1 tumor mice (P < 0.05), whereas the mean life of TXM13 tumor mice was significantly prolonged after treatment with 22.2-MBq and 37.0- MBq doses of (188)Re-(Arg(11))CCMSH (P < 0.05). High-dose (188)Re-(Arg(11))CCMSH produced no observed normal tissue toxicity.
  
  
  CONCLUSIONS
  The therapy study results revealed that (188)Re-(Arg(11))CCMSH yielded significant therapeutic effects in both B16/F1 murine melanoma- and TXM13 human melanoma-bearing mouse models. (188)Re-(Arg(11))CCMSH appears to be a promising radiolabeled peptide for targeted radionuclide therapy of melanoma.
authors.affiliation: Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65211, USA.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Miao
authors.forename: Nellie K
authors.initials: NK
authors.lastname: Owen
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Fisher
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Hoffman
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Quinn
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000532:radiotherapy*; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D012211:Rhenium / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016019:Survival Analysis; D014018:Tissue Distribution; D016896:Treatment Outcome; D000521:alpha-MSH / Q000493:pharmacokinetics* / Q000627:therapeutic use*
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; D000521:alpha-MSH; D012211:Rhenium