title: Effect of coligands on biodistribution characteristics of ternary ligand 99mTc complexes of a HYNIC-conjugated cyclic RGDfK dimer.
abstract: This report describes biodistribution characteristics of three ternary ligand complexes [(99m)Tc(SQ168)(tricine)(L)] (SQ168 = [2-[[[5-[carboonyl]-2-pyridinyl]hydrazono]methyl]-benzenesulfonic acid]-Glu(cyclo{Lys-Arg-Gly-Asp-d-Phe})-cyclo{Lys-Arg-Gly-Asp-d-Phe}; L = TPPTS (trisodium triphenylphosphine-3,3',3' '-trisulfonate), ISONIC (isonicotinic acid) and PDA (2,5-pyridinedicarboxylic acid)) in athymic nude mice bearing MDA-MB-435 human breast cancer xenografts. Ternary ligand complexes [(99m)Tc(SQ168)(tricine)(L)] (L = TPPTS, ISONIC and PDA) were prepared and were analyzed by a reversed HPLC method. Surprisingly, coligands have little impact on log P values of their ternary ligand (99m)Tc complexes even though HPLC retention times suggest that [(99m)Tc(SQ168)(tricine)(PDA)] and [(99m)Tc(SQ168)(tricine)(ISONIC)] are more hydrophilic than [(99m)Tc(SQ168)(tricine)(TPPTS)]. The results from biodistribution studies indicated that excretion kinetics of the (99m)Tc-labeled cyclic RGDfK dimer can be modified by the choice of coligand. The fact that all three radiotracers show high tumor uptake during the 2 h study period suggests that the coligand has minimal effect on the tumor targeting capability of the (99m)Tc-labeled cyclic RGDfK dimer. Results from the blocking experiment suggest that the tumor localization of the (99m)Tc-labeled cyclic RGDfK dimer is integrin alpha(v)beta(3)-mediated. On the basis of their liver uptake and tumor/liver ratios, we believe that PDA has the advantage over TPPTS and ISONIC for the (99m)Tc-labeling of HYNIC-biomolecule conjugates.
authors.affiliation: Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907, USA. lius@pharmacy.purdue.edu
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Hsieh
authors.forename: Young-Seung
authors.initials: YS
authors.lastname: Kim
authors.forename: Sulma I
authors.initials: SI
authors.lastname: Mohammed
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D013667:Technetium; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D008024:Ligands; D009842:Oligopeptides; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D013667:Technetium; C047981:arginyl-glycyl-aspartic acid