title: Synthesis and biological evaluation of a novel (177)Lu-DOTA-[Gly(3)-cyclized(Dap(4), (d)-Phe(7), Asp(10))-Arg(11)]α-MSH(3-13) analogue for melanocortin-1 receptor-positive tumor targeting.
abstract: In this study, a novel α-melanocyte stimulating hormone (α-MSH) analogue 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) coupled [Gly(3)-cyclized(Dap(4), (d)-Phe(7), Asp(10))-Arg(11)]α-MSH(3-13) (DOTA-GMSH) for melanocortin-1 receptor (MC-1R) targeting was newly synthesized, radiolabeled with (177)Lu, and in vitro and in vivo characterized. (177)Lu-labeled peptides were prepared with a high radiolabeling yield (>98%), and its Log p value was -2.89. No degradation was observed not only by serum incubation at 37°C for 7 days but also by an HPLC analysis of radioactive metabolites in urine. A cell binding assay revealed that an inhibitory concentration of 50% (IC(50)) of the peptide was 3.80 nM. The tumor-to-blood ratio, which was 14.27 at 2 hours p.i., was increased to 56.37 at 24 hours p.i., which means that the radiolabeled peptide was highly accumulated in a tumor and was rapidly cleared from the blood pool. We, therefore, conclude that (177)Lu-DOTA-GMSH has promising characteristics for application in nuclear medicine, namely for the diagnosis of MC-1R over-expressing tumors.
authors: Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute (KAERI) , Daejeon, Republic of Korea.
authors: Jae Cheong
authors: JC
authors: Lim
authors: Young Don
authors: YD
authors: Hong
authors: Jin Ju
authors: JJ
authors: Kim
authors: Sang Mu
authors: SM
authors: Choi
authors: Hye Suk
authors: HS
authors: Baek
authors: Sun-Ju
authors: SJ
authors: Choi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004355:Drug Stability; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D007553:Isotope Labeling; D008187:Lutetium / Q000737:chemistry*; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D011868:Radioisotopes / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D044102:Receptor, Melanocortin, Type 1 / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D014018:Tissue Distribution; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D006573:Heterocyclic Compounds, 1-Ring; D009842:Oligopeptides; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D044102:Receptor, Melanocortin, Type 1; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D000521:alpha-MSH; D008187:Lutetium