Impact of PKM linkers on biodistribution characteristics of the 99mTc-labeled cyclic RGDfK dimer.
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).
Liu
Shuang
S
School of Health Sciences, Purdue University, 550 Stadium Mall Drive, West Lafayette, Indiana 47907, USA. lius@pharmacy.purdue.edu
He
Zhengjie
Z
Hsieh
Wen-Yuan
WY
Kim
Young-Seung
YS
Jiang
Young
Y
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
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