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.