In vivo detection of d‐amino acid oxidase with hyperpolarized d‐[1‐¹³C]alanine.

Radaelli, Alice; Gruetter, Rolf; Yoshihara, Hikari A. I.

d‐amino acid oxidase (DAO) is a peroxisomal enzyme that catalyzes the oxidative deamination of several neutral and basic d‐amino acids to their corresponding α‐keto acids. In most mammalian species studied, high DAO activity is found in the kidney, liver, brain and polymorphonuclear leukocytes, and its main function is to maintain low circulating d‐amino acid levels. DAO expression and activity have been associated with acute and chronic kidney diseases and with several pathologies related to N‐methyl‐d‐aspartate (NMDA) receptor hypo/hyper‐function; however, its precise role is not completely understood. In the present study we show that DAO activity can be detected in vivo in the rat kidney using hyperpolarized d‐[1‐13C]alanine. Following a bolus of hyperpolarized d‐alanine, accumulation of pyruvate, lactate and bicarbonate was observed only when DAO activity was not inhibited. The measured lactate‐to‐d‐alanine ratio was comparable to the values measured when the l‐enantiomer was injected. Metabolites downstream of DAO were not observed when scanning the liver and brain. The conversion of hyperpolarized d‐[1‐13C]alanine to lactate and pyruvate was detected in blood ex vivo, and lactate and bicarbonate were detected on scanning the blood pool in the heart in vivo; however, the bicarbonate‐to‐d‐alanine ratio was significantly lower compared with the kidney. These results demonstrate that the specific metabolism of the two enantiomers of hyperpolarized [1‐13C]alanine in the kidney and in the blood can be distinguished, underscoring the potential of d‐[1‐13C]alanine as a probe of d‐amino acid metabolism.

ALANINE; LACTATES; CHRONIC kidney failure

NMR in Biomedicine, 2020, Vol 33, Issue 7, p1

0952-3480

Academic Journal

10.1002/nbm.4303