Deuterium MetabolicImaging of the Brain Using 2‑Deoxy-2‑[²H₂]‑d‑glucose: A Non-ionizing[¹⁸F]FDG Alternative

The positron emission tomography (PET) tracer 2-deoxy-2-[¹⁸F]fluoroglucose ([¹⁸F]FDG) is widely used to study diseases where glucose metabolism is dysregulated, including cancer and neurodegenerative disorders. Here we investigate the hypothesis that the 2-position deuterium-enriched analogue 2-deoxy-2-[²H₂]-d-glucose (2-DG-d2) can also map glucose uptake using deuterium metabolic imaging (DMI) without ionizing radiation. To accomplish this, we used a spectrally selective multiband radiofrequency pulse and balanced steady-state free procession (bSSFP) technique, enabling rapid ²H imaging with high specificity and sensitivity to 2-DG-d2. Both <i>in vitro</i> and <i>in vivo</i> validations demonstrated the sequence’s ability to suppress endogenous water signal. Mapping of 2-DG-d2 with high spatial resolution was achieved in healthy mouse brains, comparable to what might be obtained using [¹⁸F]FDG PET. The numerous applications of [¹⁸F]FDG PET, as well as recent clinical translation of the natural abundance 2-deoxy-d-glucose (2-DG) parent sugar, suggest that DMI using 2-DG-d2 may be applied to patients in the future.