Radiolabeling and Biological Evaluation of Novel 99mTc-Nitrido and 99mTc-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 Tc-99m-labeled complexes ([Tc-99m]TcN-MOPADTC and [Tc-99m]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; [Tc-99m]TcO-MOPADTC is hydrophilic, while [Tc-99m]TcN-MOPADTC is slightly lipophilic. The biodistribution of [Tc-99m]TcN-MOPADTC and [Tc-99m]TcO-MOPADTC in mice bearing S180 tumors shows that the tumor uptake and tumor/muscle ratio of [Tc-99m]TcO-MOPADTC were higher than the tumor uptake and tumor/muscle ratio of [Tc-99m]TcN-MOPADTC. In addition, the tumor retention of [Tc-99m]TcO-MOPADTC is better than the tumor retention of [Tc-99m]TcN-MOPADTC. A competitive inhibition assay was performed, and the results indicate that [Tc-99m]TcO-MOPADTC may enter cells primarily via the (L)-alanine/(L)-serine/(L)-cysteine (ASC) system. Single-photon emission computed tomography (SPECT) imaging of [Tc-99m]TcO-MOPADTC shows obvious accumulation in tumor sites, suggesting that [Tc-99m]TcO-MOPADTC is a novel potential tumor-imaging agent.

Automated summary

The study focuses on the development of novel radiolabeled amino acid tumor imaging agents and evaluates the in vitro stability, partition coefficient, and biodistribution of two Tc-99m-labeled complexes. The results demonstrate that [Tc-99m]TcO-MOPADTC shows higher tumor uptake, tumor/muscle ratio, and tumor retention compared to [Tc-99m]TcN-MOPADTC. The competitive inhibition assay provides insights into the cellular entry mechanism of [Tc-99m]TcO-MOPADTC.