Radiolabeling and Biological Evaluation of Novel 99m Tc-Nitrido and 99m Tc-Oxo Complexes with 4-Methoxy- L -Phenylalanine Dithiocarbamate for Tumor Imaging.

To develop novel radiolabeled amino acid tumor imaging agents, 4-methoxy- L -phenylalanine dithiocarbamate (MOPADTC) was synthesized successfully, and two kinds of 99m Tc-labeled complexes ([ 99m Tc]TcN-MOPADTC and [ 99m Tc]TcO-MOPADTC) with high radiochemical purities (RCP > 95%) were obtained. The in vitro stability and partition coefficient were determined, and the results show that both of these complexes have good in vitro stability; [ 99m Tc]TcO-MOPADTC is hydrophilic, while [ 99m Tc]TcN-MOPADTC is slightly lipophilic. The biodistribution of [ 99m Tc]TcN-MOPADTC and [ 99m Tc]TcO-MOPADTC in mice bearing S180 tumors shows that the tumor uptake and tumor/muscle ratio of [ 99m Tc]TcO-MOPADTC were higher than the tumor uptake and tumor/muscle ratio of [ 99m Tc]TcN-MOPADTC. In addition, the tumor retention of [ 99m Tc]TcO-MOPADTC is better than the tumor retention of [ 99m Tc]TcN-MOPADTC. A competitive inhibition assay was performed, and the results indicate that [ 99m Tc]TcO-MOPADTC may enter cells primarily via the L -alanine/ L -serine/ L -cysteine (ASC) system. Single-photon emission computed tomography (SPECT) imaging of [ 99m Tc]TcO-MOPADTC shows obvious accumulation in tumor sites, suggesting that [ 99m Tc]TcO-MOPADTC is a novel potential tumor-imaging agent.