Synthesis and evaluation of a new class of technetium-99m monocationic radiotracers from dithienyldiazalkanes

Abstract

Monocationic 99mTc complexes, [ 99mTcO 2(THEN)] + and [ 99mTcO 2(THPN)] + derived from a new class of N 2S 2 chelators diethienyldiazalkanes, namely 1,6-di(2-thienyl)-2,5-diazahexane (THEN) and 1 7-di-(2-thienyl)-4,4-dimethyl-2,6-diazaheptane (THPN), have been synthesized using Sn(II) tartrate reduction of [ 99mTc]pertechnetate at pH 9 and extraction of the complexes as ion pairs with trifluoromethane sulfonate anion (CF 3SO 3 −) in high radiochemical yield (~90%). Radiochemical analysis of the 99mTc complexes using chromatography (Whatman Cellulose CEL300 DEAE anion exchange strip, MEK) and paper chromatography (Whatman I, acetone) revealed high radiochemical purity (>90%). High octanol-saline partition coefficients (>37) of [ 99mTcO 2THEN)] + and [ 99mTcO 2(THPN)] + indicated a lipophilic nature of the complexes. Relative stability of the 99mTc complex was high as measured by DTPA challenge studies. Biodistribution of [ 99mTcO 2(THEN)] + and [ 99mTcO 2(THPN)] + in rats at 15 min post-injection showed heart-to-blood activity ratios of 0.26 and 0.46, respectively, with rapid blood clearance. Further studies involving the variation of substituents on the basic core structure of this new class of 99mTc complexes may provide radiotracers suitable for myocardial imaging.