NIMG-32. ORAL ADMINISTRATION OF DEUTERATED CHOLINE AS A NEW APPROACH TO PROVIDE HIGH TUMOR-TO-BRAIN IMAGE CONTRAST IN DEUTERIUM METABOLIC IMAGING (DMI)

Abstract BACKGROUND Metabolic imaging using FDG-PET is a key component of disease management in many cancers outside of the brain, but in brain tumors it often shows low tumor-to-brain contrast because of high background signal from normal brain. We explore generating cancer-specific metabolic image contrast using Deuterium Metabolic Imaging (DMI), which is a novel 2H magnetic resonance spectroscopic imaging-based technique. DMI was applied after oral administration of deuterated choline, an essential nutrient needed for membrane synthesis whose uptake is often increased in tumors. METHODS Total choline (tCho) DMI was performed in an orthotopic model of glioblastoma, F344 rats (n=11) implanted with RG2 cells, on an 11.7 tesla MRI scanner, with isotropic spatial resolution of 2.5 mm. tCho-DMI data were collected for 36 min during intravenous infusion (IV, n=6) or after 3 days of oral administration (PO, n=5) of [2H9]-choline chloride dissolved in sterile water. At a dose of 285 mg/kg body weight, bolus-continuous IV infusion via the tail vein required 1.57 ml for a 250-gram rat. PO administration via gavage on 3 consecutive days used the max daily dose recommended for human adults, 50 mg/kg. Results - In the PO group, average tumor tCho concentration was 0.78±0.14 mM and 0.20±0.05 mM in contralateral normal brain. In the IV group, the tCho concentration was 0.88±0.18 mM in the tumor, and 0.18±0.03 mM in normal brain (PO vs. IV: p=0.52). Tumor-to-brain contrast was 5.9±1.2 in PO-administered animals, and 7.1±3.3 for animals receiving IV 2H-choline, (p=0.54). CONCLUSIONS - In a preclinical GBM model oral administration of [2H9]-choline resulted in comparably high tumor-to-brain image contrast on tCho-DMI-based maps as during IV infusion. Work is ongoing to identify the different choline metabolites that contribute to the tCho signal. Because oral administration of choline is very safe, this approach could facilitate the translation of tCho-DMI to human subjects.