Contribution of labeled carbon dioxide to PET imaging of carbon-11-labeled compounds

¹¹CO₂ is one of the major metabolites of many [¹¹C]-labeled radiopharmaceuticals, including glucose, thymidine, acetate, amino acids, and fatty acids. Our data contradict the notion that the contribution of labeled CO₂ to PET images can be disregarded because of its rapid elimination through the lungs. We have measured the retention and excretion of ¹¹CO₂ in dogs after the intravenous injection of labeled CO₂/HCO₃^-, which had been equilibrated ex vivo with blood. Only 58% of the label was exhaled as CO₂ over the first 60 min after injection, with the rest retained in the body. The injection of [¹¹C]thymidine labeled in the ring-2 position or [¹¹C]acetate labeled in the carboxylate position resulted in the production of large amounts of labeled CO₂ with the exhalation of about 47% and 23%, respectively, of the injected label over 60 min. At 10 min after injection of either [¹¹C]thymidine and [¹¹C]acetate, approximately 60% to 70% of total blood activity was in labeled CO₂ or bicarbonate. On the other hand, the use of [1-¹¹C]glucose only resulted in exhalation of 5% of the injected dose and CO₂/HCO₃^- made up <10% of blood activity at 10 min. Our results indicate that retention and distribution of labeled CO₂ needs to be considered when interpreting PET data obtained from ¹¹C-labeled compounds.