Article ID Journal Published Year Pages File Type
2154477 Nuclear Medicine and Biology 2008 11 Pages PDF
Abstract

In this study, we present the evaluation of two new ternary ligand 99mTc complexes [99mTc(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 [99mTc(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 [99mTc(HYNIC tetramer)(tricine)(PDA)] had a much lower uptake in most organs of interest than [99mTc(HYNIC tetramer)(tricine)(ISONIC)] during the 2-h study period. Results from metabolism studies revealed that ∼50% of [99mTc(HYNIC tetramer)(tricine)(ISONIC)] remained intact in fecal samples at 120 min postinjection, whereas only 10% of [99mTc(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 99mTc-labeled cyclic RGDfK tetramer. Among the three radiotracers evaluated in this tumor-bearing animal model, [99mTc(HYNIC tetramer)(tricine)(TPPTS)] remained the best with respect to blood clearance, tumor uptake and target/background ratios.

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