Radical‐free hyperpolarized MRI using endogenously occurring pyruvate analogues and UV‐induced nonpersistent radicals.

Zanella, Claudia C.; Capozzi, Andrea; Yoshihara, Hikari A. I.; Radaelli, Alice; Mackowiak, Adèle L. C.; Arn, Lionel P.; Gruetter, Rolf; Bastiaansen, Jessica A. M.

It was recently demonstrated that nonpersistent radicals can be generated in frozen solutions of metabolites such as pyruvate by irradiation with UV light, enabling radical‐free dissolution dynamic nuclear polarization. Although pyruvate is endogenous, the presence of pyruvate may interfere with metabolic processes or the detection of pyruvate as a metabolic product, making it potentially unsuitable as a polarizing agent. Therefore, the aim of the current study was to characterize solutions containing endogenously occurring alternatives to pyruvate as UV‐induced nonpersistent radical precursors for in vivo hyperpolarized MRI. The metabolites alpha‐ketovalerate (αkV) and alpha‐ketobutyrate (αkB) are analogues of pyruvate and were chosen as potential radical precursors. Sample formulations containing αkV and αkB were studied with UV–visible spectroscopy, irradiated with UV light, and their nonpersistent radical yields were quantified with electron spin resonance and compared with pyruvate. The addition of 13C‐labeled substrates to the sample matrix altered the radical yield of the precursors. Using αkB increased the 13C‐labeled glucose liquid‐state polarization to 16.3% ± 1.3% compared with 13.3% ± 1.5% obtained with pyruvate, and 8.9% ± 2.1% with αkV. For [1–13C]butyric acid, polarization levels of 12.1% ± 1.1% for αkV, 12.9% ± 1.7% for αkB, 1.5% ± 0.2% for OX063 and 18.7% ± 0.7% for Finland trityl, were achieved. Hyperpolarized [1–13C]butyrate metabolism in the heart revealed label incorporation into [1–13C]acetylcarnitine, [1–13C]acetoacetate, [1–13C]butyrylcarnitine, [5‐13C]glutamate and [5‐13C]citrate. This study demonstrates the potential of αkV and αkB as endogenous polarizing agents for in vivo radical‐free hyperpolarized MRI. UV‐induced, nonpersistent radicals generated in endogenous metabolites enable high polarization without requiring radical filtration, thus simplifying the quality‐control tests in clinical applications.

FINLAND; PYRUVATES; ELECTRON paramagnetic resonance; POLARIZATION (Nuclear physics); MAGNETIC resonance imaging; BUTYRIC acid

NMR in Biomedicine, 2021, Vol 34, Issue 11, p1

0952-3480

Academic Journal

10.1002/nbm.4584