Radiolabeling and Biological Evaluation of Novel ^99mTc-Nitrido and ^99mTc-Oxo Complexes with 4-Methoxy-_L-Phenylalanine Dithiocarbamate for Tumor Imaging.

ABSTRACT: To develop novel radiolabeled amino acid tumor imaging agents, 4-methoxy-_L-phenylalanine dithiocarbamate (MOPADTC) was synthesized successfully, and two kinds of ^99mTc-labeled complexes ([^99mTc]TcN-MOPADTC and [^99mTc]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; [^99mTc]TcO-MOPADTC is hydrophilic, while [^99mTc]TcN-MOPADTC is slightly lipophilic. The biodistribution of [^99mTc]TcN-MOPADTC and [^99mTc]TcO-MOPADTC in mice bearing S180 tumors shows that the tumor uptake and tumor/muscle ratio of [^99mTc]TcO-MOPADTC were higher than the tumor uptake and tumor/muscle ratio of [^99mTc]TcN-MOPADTC. In addition, the tumor retention of [^99mTc]TcO-MOPADTC is better than the tumor retention of [^99mTc]TcN-MOPADTC. A competitive inhibition assay was performed, and the results indicate that [^99mTc]TcO-MOPADTC may enter cells primarily via the _L-alanine/_L-serine/_L-cysteine (ASC) system. Single-photon emission computed tomography (SPECT) imaging of [^99mTc]TcO-MOPADTC shows obvious accumulation in tumor sites, suggesting that [^99mTc]TcO-MOPADTC is a novel potential tumor-imaging agent.

SUBMITTER: Yin G 

PROVIDER: S-EPMC9607073 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature