title: 99mTc-tricarbonyl labeled agents for cell labeling: development, biodistribution in normal mice and preliminary in vitro evaluation.
abstract: We have developed four (99m)Tc(CO)(3)-labeled lipophilic tracers as potential radiolabeling agents for cells based on a hexadecyl tail. (99m)Tc(CO)(3)-hexadecylamino-N,N'-diacetic acid (negatively charged), (99m)Tc(CO)(3)-hexadecylamino-N-alpha-picolyl-N'-acetic acid (uncharged), (99m)Tc(CO)(3)-N,N'-dipicolylhexadecylamine (positively charged), (99m)Tc(CO)(3)-N-hexadecylaminoethyl-N'-aminoethylamine (positively charged) were prepared in a radiolabeling yield: >90%. Preliminary cell uptake studies were performed in mixed blood cells with or without plasma and were compared with (99m)Tc-d,l-HMPAO and [(18)F]FDG. In plasma-free blood cells, maximum uptake (78%) was obtained for (99m)Tc(CO)(3)-N-hexadecylaminoethyl-N'-aminoethylamine after 60min incubation (compared to 55% and 23% for (99m)Tc-d,l-HMPAO and [(18)F]FDG, respectively) while in plasma-rich medium, (99m)Tc(CO)(3)-N,N'-dipicolylhexadecylamine was best bound (54%, similar to the binding of (99m)Tc-d,l-HMPAO). Biodistribution in normal mice showed mainly hepatobiliary clearance of the agents and initial high lung uptake. The radiolabeled compounds showed good blood clearance with maximally 7.9% injected dose per gram at 60 min post injection. While the least lipophilic agent ((99m)Tc(CO)(3)-N,N'-dipicolylhexadecylamine, logP=1.3) showed the best cell uptake, there appears to be no direct correlation between lipophilicity and tracer uptake in mixed blood cells. In view of its comparable cell uptake to well known cell labeling agent (99m)Tc-d,l-HMPAO, (99m)Tc(CO)(3)-N,N'-dipicolylhexadecylamine merits further evaluation as a potential cell labeling agent.
authors.affiliation: Laboratory for Radiopharmacy, Faculty of Pharmaceutical Sciences, KU Leuven, BE-3000 Leuven, Belgium. humphrey.fonge@utoronto.ca
authors.forename: Humphrey
authors.initials: H
authors.lastname: Fonge
authors.forename: Lixin
authors.initials: L
authors.lastname: Jin
authors.forename: Jan
authors.initials: J
authors.lastname: Cleynhens
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.forename: Alfons
authors.initials: A
authors.lastname: Verbruggen
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003584:Cytological Techniques; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D013667:Technetium / Q000737:chemistry* / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D008055:Lipids; D013667:Technetium