title: Evaluation of the human melanoma targeting properties of radiolabeled alpha-melanocyte stimulating hormone peptide analogues.
abstract: The purpose of this study was to evaluate the human MC1 receptor-mediated melanoma targeting properties of two metal cyclized alpha-MSH peptide analogues, (188)Re-(Arg(11))CCMSH and (188)Re-CCMSH. Initially, the presence and density of the MC1 receptor were determined on a bank of human melanoma cell lines. All eight human melanoma cell lines tested in this study displayed the MC1 receptor at a density of 900 to 5700 receptors per cell. Receptor affinity and biodistribution properties of (188)Re-(Arg(11))CCMSH and (188)Re-CCMSH were evaluated in a cultured TXM13 human melanoma-xenografted Scid mouse model. Biodistribution results demonstrated that 3.06 +/- 0.68 %ID/g of (188)Re-(Arg(11))CCMSH accumulated in the tumors 1 h postinjection and greater than 65% of the activity at 1 h postinjection remained in the tumors at 4 h after dose administration. Whole body clearance of (188)Re-(Arg(11))CCMSH was very rapid, with approximately 82% of injected dose cleared through urinary system at 4 h postinjection. There was very little activity in blood and major organs such as liver, lung, and muscle except for the kidney. (188)Re-CCMSH exhibited similar tumor uptake and retention in TXM13 human melanoma-xenografted Scid mice as (188)Re-(Arg(11))CCMSH. However, the kidney uptake value of (188)Re-CCMSH was two times higher than that of (188)Re-(Arg(11))CCMSH. The results of this study indicate that the MC1 receptor is present on the surface of a large number of human melanoma cells, which makes the MC1 receptor a good imaging or therapeutic target. Moreover, the biodistribution properties of (188)Re-(Arg(11))CCMSH and (188)Re-CCMSH highlight their potential as therapeutic agents for human melanoma.
authors: Department of Biochemistry, University of Missouri-Columbia, Columbia, Missouri 65211, USA.
authors: Yubin
authors: Y
authors: Miao
authors: Donna
authors: D
authors: Whitener
authors: Weiwei
authors: W
authors: Feng
authors: Nellie K
authors: NK
authors: Owen
authors: Jianqing
authors: J
authors: Chen
authors: Thomas P
authors: TP
authors: Quinn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism*; D012211:Rhenium / Q000378:metabolism* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: C487558:Ac-Cys-Cys-Glu-His-D-Phe-Arg-Trp-Cys-Lys-Pro-Val-NH2; D000970:Antineoplastic Agents; D015609:Organotechnetium Compounds; D010446:Peptide Fragments; D044102:Receptor, Melanocortin, Type 1; D012211:Rhenium