Analysis of 2-carbon-11-thymidine blood metabolites in PET imaging

Carbon-11-thymidine labeled in the ring-2 position was used with PET to image tumor and tissue proliferation. Since thymidine is rapidly degraded in the body, one must consider the generation of metabolites to fully interpret the PET data. Methods: We have measured the blood time-activity curves of thymidine and its metabolites in arterial blood samples. Blood was processed to obtain three input curves, including the total activity, the activity with CO₂ removed and the fraction of CO₂-free activity in intact thymidine (% Tdr). Results: We found that CO₂ reached a plateau of 65% (±12%) of total blood activity by 11 min after injection. When a 1-min infusion of labeled thymidine is used, the time to 50% degradation to thymine and metabolites other than CO₂ (measured in acidified samples by HPLC) was 2.9 ± 0.6 min. We fit the results of the blood metabolism with a compartmental model. We found that we could accurately determine the %Tdr curve with as few as three measured points with an root mean square (RMS) error of 2% in the integrated curve, compared to the curve using all blood samples (mean of seven samples per patient). The integral of thymidine blood activity serves as the input to thymidine models, so similar errors could be expected in calculations of DNA synthetic rates. We found that the determination of CO₂ could be accomplished with as few as five samples, with an RMS error of 4% in plateau %CO₂ value. Conclusion: While it is essential to take metabolites into account when interpreting results obtained with ¹¹C-thymidine, the reproducibility of these degradation curves may allow the use of a limited number of samples to measure the catabolic products of thymidine. These data from the blood, along with tissue kinetic models, are needed to calculate DNA synthetic rates.