title: Impact of PKM linkers on biodistribution characteristics of the 99mTc-labeled cyclic RGDfK dimer.
abstract: This report describes synthesis of three new cyclic RGDfK peptide conjugates, HYNIC-PKM-SU016 (PKM = E, K and PEG4) and in vivo evaluation of the impact of PKM linkers on biodistribution characteristics of their ternary ligand complexes [99mTc(HYNIC-PKM-SU016)1(tricine)(TPPTS)] in athymic nude mice bearing the MDA-MB-435 human breast cancer xenografts. Results from biodistribution studies show that PKM linkers have minimal impact on the integrin alphavbeta3 binding capability of radiotracers. Even though they have different charges under physiological conditions, all three linkers (E, K, and PEG4) are able to reduce the uptake of 99mTc-labeled E[c(RGDfK)]2 in blood, kidneys, liver, and lungs, and increase target-to-background (T/B) ratios at >30 min postinjection. E and K may have advantages over PEG4 due to a combination of relatively low liver uptake and high tumor/liver and tumor/lung ratios of ternary ligand complexes [99mTc(HYNIC-PKM-SU016)(tricine)(TPPTS)] (PKM = E and K).
authors.affiliation: School of Health Sciences, Purdue University, 550 Stadium Mall Drive, West Lafayette, Indiana 47907, USA. lius@pharmacy.purdue.edu
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.forename: Zhengjie
authors.initials: Z
authors.lastname: He
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Hsieh
authors.forename: Young-Seung
authors.initials: YS
authors.lastname: Kim
authors.forename: Young
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000737:chemistry*; D019281:Dimerization; D018698:Glutamic Acid / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D008239:Lysine / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013667:Technetium; D023041:Xenograft Model Antitumor Assays
chemical_list: C516050:15-amino-4,7,10,13-tetraoxapentadecanoic acid; D003432:Cross-Linking Reagents; D008024:Ligands; D010456:Peptides, Cyclic; C099250:cyclic (arginyl-glycyl-aspartyl-phenylalanyl-lysyl); D018698:Glutamic Acid; D011092:Polyethylene Glycols; D013667:Technetium; D008239:Lysine