Preparation and biological evaluation of 99m TcN‐4‐(cyclohexylpiperazin‐1‐yl)‐dithioformate as a potential sigma receptor imaging agent

The goal of this study is to develop a novel 99m Tc‐labeled σ receptor imaging agent. Potassium 4‐(cyclohexylpiperazin‐1‐yl)‐dithioformate, 2 , and the corresponding rhenium complex, ReN‐2 , were synthesized and characterized. ReN‐2 possessed moderate affinity toward σ 1 (K i = 1.94 ± 0.60 µmol/L) and σ 2 (K i = 2.83 ± 1.39 µmol/L) receptors. The radiolabeled complex 99m TcN‐2 was prepared in high yield (> 95%) through the [ 99m TcN]   int 2+precursor and characterized by HPLC. 99m TcN‐2 was found to be a lipophilic and neutral complex with good stability. The biodistribution in tumor‐bearing mice showed that 99m TcN‐2 had good tumor uptake (2.12 ± 0.01 %ID/g at 2 h p.i.) and moderate brain uptake (0.27 ± 0.05 %ID/g at 2 h p.i.). After blocking with haloperidol, the uptakes by tumor and brain were lower than control. The results indicated that the complex has specific binding to the σ receptors in vivo . Further structural modifications of this complex are needed to obtain 99m Tc‐based σ receptor imaging agents with high affinity and subtype selectivity. Copyright © 2007 John Wiley & Sons, Ltd.