Introduction: We recently evaluated that 4 -[methyl-14 C]thiothymidine ([methyl-14 C]S-dThd) is a novel thymidine analog for simplified 11 C-PET imaging of DNA synthesis in cell proliferation (Toyohara et al., J Nucl Med 2006; 47:1717-1722). Our results suggest that [methyl-14 C]S-dThd closely resembles the biochemistry in anabolic metabolism and might be used as an alternative to [2-11 C]thymidine. Here, we carried out 11 C-labeling of 4 -thiothymidine and evaluated the feasibility of using the tracer to image cellular proliferation by PET. Experimental: [Methyl-11 C]S-dThd was synthesized by rapid methylation of 5-trimethylstannyl-precursor via a palladium mediated Stille coupling reaction with 11 C-methyl iodide. Resultant [methyl-11 C]S-dThd was purified by the semi-preparative HPLC. The in vivo potential of [methyl-11 C]S-dThd was evaluated by studying its biodistribution in EMT-6 tumor-bearing mice. A dynamic scan was performed in mice with a microPET scanner.
Results and Discussion: A simple one-pot synthesis produced >20 mCi (740 MBq) of radiochemically pure [methyl-11 C]S-dThd, with a specific activity >15GBq/ฮผmol at 30 min after end of bomberdment (EOB) and 25% radiochemical yield (EOB); 7% end of synthesis (EOS). At 60 min after injection, [methyl-11 C]S-dThd uptake was highest in the proliferating tissues (mean SUVs: spleen, 6.2; tumor, 1.6; thymus, 1.1), whereas the non-proliferative tissues showed little uptake (mean SUVs: liver, 1.0; kidney, 0.6; lung, 0.4; muscle, 0.3; heart, 0.3). MicroPET imaging cleary demonstrated high uptake in the proliferating tissues such as tumor and marrow. The dynamic analysis showed accumulative uptake of the tracer in tumor over 60 min.
Conclusion:
These results indicate that [methyl-11 C]S-dThd may useful for measuring DNA synthesis with PET. Acknowledgement: We also thank the crew of the Cyclotron Operation Section and Radiopharmaceutical Cemistry Section of National Institute of Radiological Sciences for their support in the operation of the cyclotron and production of radioisotopes.