Synthesis of [1-¹³C]2-Oxoglutaric Acid and ¹³C Breath Tests Designed to Assess TCA Cycle Flux

Several approaches for synthesizing [1-¹³C]2-oxoglutaric acid were attempted, and the synthesis was successfully achieved in 4 steps from trimethylsilyl ¹³C-cyanide. The ¹³C-breath tests on rats were conducted by orally administering the newly synthesized [1-¹³C]2-oxoglutaric acid, the previously prepared [1'-¹³C]citric acid, and [1-¹³C]acetic acid as a control drug, and the results were compared. The results indicate that [1-¹³C]2-oxoglutaric acid and [1'-¹³C]citric acid may serve as potential substrates for assessing the TCA cycle flux.