In this study, we present the evaluation of two new ternary
ligand (99m)Tc complexes [(99m)Tc(HYNIC tetramer)(
tricine)(L)] [L=
isonicotinic acid (ISONIC) and
2,5-pyridinedicarboxylic acid (PDA)] as potential radiotracers for
tumor imaging. Athymic nude mice bearing MDA-MB-435 human
breast cancer xenografts were used to evaluate their biodistribution and metabolic properties.
Solution stability data showed that [(99m)Tc(HYNIC tetramer)(
tricine)(L)] (L=ISONIC and PDA) had significant decomposition (14% and 35%, respectively) at 6 h in the absence of excess ISONIC or PDA coligand. Biodistribution data clearly showed that [(99m)Tc(HYNIC tetramer)(
tricine)(PDA)] had a much lower uptake in most organs of interest than [(99m)Tc(HYNIC tetramer)(
tricine)(ISONIC)] during the 2-h study period. Results from metabolism studies revealed that approximately 50% of [(99m)Tc(HYNIC tetramer)(
tricine)(ISONIC)] remained intact in fecal samples at 120 min postinjection, whereas only 10% of [(99m)Tc(HYNIC tetramer)(
tricine)(PDA)] remained intact in fecal samples. The extent of metabolism correlated well with radiotracer
solution stability. The results from this and our previous studies clearly demonstrated that coligands [trisodium triphenylphosphine-3,3',3''-trisulfonate (TPPTS), ISONIC and PDA] have a significant impact on the
tumor uptake, excretion kinetics and metabolism of the (99m)Tc-labeled
cyclic RGDfK tetramer. Among the three radiotracers evaluated in this
tumor-bearing animal model, [(99m)Tc(HYNIC tetramer)(
tricine)(TPPTS)] remained the best with respect to blood clearance,
tumor uptake and target/background ratios.