SYNTHESIS AND EVALUATION OF A NEW CLASS OF TC-99M MONOCATIONIC RADIOTRACERS FROM DITHIENYLDIAZALKANES

Monocationic Tc-99m complexes, [(TcO2)-Tc-99m(THEN)](+) and [(TcO2)-Tc -99m(THPN)](+) derived from a new class of N2S2 chelators diethienyldi azalkanes, 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 synthesi zed using Sn(II) tartrate reduction of [Tc-99m]pertechnetate at pH 9 a nd extraction of the complexes as ion pairs with trifluoromethane sulf onate anion (CF3SO3-) in high radiochemical yield (similar to 90%). Ra diochemical analysis of the (?)(99m)Tc complexes using chromatography (Whatman Cellulose CEL300 DEAF anion exchange strip, MEK) and paper ch romatography (Whatman I, acetone) revealed high radiochemical purity ( >90%). High octanol-saline partition coefficients (> 37) of [(TcO2)-Tc -99m(THEN)](+) and [(TcO2)-Tc-99m(-THPN)]+ indicated a lipophilic natu re of the complexes. Relative stability of the Tc-99m complex was high as measured by DTPA challenge studies. Biodistribution of [(TcO2)-Tc- 99m(THEN)](+) and [(TcO2)-Tc-99m(THPN)](+) in rats at 15 min post-inje ction showed heart-to-blood activity ratios of 0.26 and 0.46, respecti vely, with rapid blood clearance. Further studies involving the variat ion of substituents on the basic core structure of this new class of ( 99)mTc complexes may provide radiotracers suitable for myocardial imag ing.