Novel Tc-labelled complexes with thymidine isocyanide: radiosynthesis and evaluation as potential tumor imaging tracers

• Published in: MedChemComm 2018-04, Vol.9 (4), p.75-712
• Main Authors: Duan, Xiaojiang, Zhang, Xuran, Gan, Qianqian, Fang, Si'an, Ruan, Qing, Song, Xiaoqing, Zhang, Junbo
• Format: Article
• Language: English
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c7md00635g

A novel thymidine isocyanide (CN-TdR) functionalized at the N3 position of thymidine was synthesized and then radiolabelled with 99m Tc( i ) and [ 99m Tc( i )(CO) 3 ] + cores to produce [ 99m Tc(CN-TdR) 6 ] + and [ 99m Tc(CO) 3 (CN-TdR) 3 ] + , respectively. Both of them were prepared with high radiochemical purity and were stable over 6 h in saline at ambient temperature and in serum at 37 °C. The partition coefficient results demonstrated that they were hydrophilic. The cell internalization studies showed that their uptake might be mediated by nucleoside transporters. Biodistribution of these complexes in mice bearing the S180 tumor showed that they accumulated in the tumor with high uptake and cleared rapidly from blood and muscles, producing high tumor/blood and tumor/muscle ratios. Between them, [ 99m Tc(CN-TdR) 6 ] + exhibited advantages concerning a higher tumor uptake, tumor/blood ratio and tumor/muscle ratio at 60 min post-injection. Single photon emission computed tomography imaging studies showed that there was a clear accumulation in tumor sites, suggesting that [ 99m Tc(CN-TdR) 6 ] + could be a promising candidate for tumor imaging. SPECT/CT image of 12 in mice bearing S180 at 1 h p.i.