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The purpose of this study was to investigate the hyperpolarized ketone body ¹³C‐acetoacetate (AcAc) and its conversion to ¹³C‐β‐hydroxybutyrate (βOHB) in vivo, catalyzed by β‐hydroxybutyrate dehydrogenase (BDH), as a novel direct marker of mitochondrial redox state.

[1,3‐¹³C₂]AcAc was synthesized by hydrolysis of the ethyl ester, and hyperpolarized via dissolution DNP. Cold storage under basic conditions resulted in sufficient chemical stability for use in hyperpolarized (HP) MRI studies. Polarizations and relaxation times of HP [1,3‐¹³C₂]AcAc were measured in a clinical 3T MRI scanner, and 8 rats were scanned by dynamic HP ¹³C MR spectroscopy of a slab through the kidneys. Four rats were scanned after acute treatment with high dose metformin (125 mg/kg, intravenous), which is known to modulate mitochondrial redox via inhibition of mitochondrial complex I. An additional …