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 -α-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 60 min 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, log  P  = 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.