Simultaneous Recording of the Uptake and Conversion of Glucose and Choline in Tumors by Deuterium Metabolic Imaging

Increased glucose and choline uptake are hallmarks of cancer. We investigated whether the uptake and conversion of [H-2(9)]choline alone and together with that of [6,6'-H-2(2)]glucose can be assessed in tumors via deuterium metabolic imaging (DMI) after administering these compounds. Therefore, tumors with human renal carcinoma cells were grown subcutaneously in mice. Isoflurane anesthetized mice were IV infused in the MR magnet for similar to 20 s with similar to 0.2 mL solutions containing either [H-2(9)]choline (0.05 g/kg) alone or together with [6,6'-H-2(2)]glucose (1.3 g/kg). H-2 MR was performed on a 11.7T MR system with a home-built H-2/H-1 coil using a 90 degrees excitation pulse and 400 ms repetition time. 3D DMI was recorded at high resolution (2 x 2 x 2 mm) in 37 min or at low resolution (3.7 x 3.7 x 3.7 mm) in 2:24 min. Absolute tissue concentrations were calculated assuming natural deuterated water [HOD] = 13.7 mM. Within 5 min after [H-2(9)]choline infusion, its signal appeared in tumor spectra representing a concentration increase to 0.3-1.2 mM, which then slowly decreased or remained constant over 100 min. In plasma, [H-2(9)]choline disappeared within 15 min post-infusion, implying that its signal arises from tumor tissue and not from blood. After infusing a mixture of [H-2(9)]choline and [6,6'-H-2(2)]glucose, their signals were observed separately in tumor H-2 spectra. Over time, the [H-2(9)]choline signal broadened, possibly due to conversion to other choline compounds, [[6,6'-H-2(2)]glucose] declined, [HOD] increased and a lactate signal appeared, reflecting glycolysis. Metabolic maps of H-2 compounds, reconstructed from high resolution DMIs, showed their spatial tumor accumulation. As choline infusion and glucose DMI is feasible in patients, their simultaneous detection has clinical potential for tumor characterization.

Automated summary

The study investigated the uptake and conversion of [H-2(9)]choline and [6,6'-H-2(2)]glucose in tumors using deuterium metabolic imaging. Results showed that the signals of these compounds could be observed separately in tumor H-2 spectra, with choline signal increasing initially and then decreasing or remaining stable, while glucose signal declined over time. This research suggests that simultaneous detection of choline and glucose in tumors has clinical potential for tumor characterization.