In vivodeuterated water labeling allows tumor visualization via deuterium magnetic resonance spectroscopic imaging of cholesterol

Abstract

AbstractWater is an essential component of many biochemical reactions. Deuterated water (D2O) has been used to study cell kinetics, protein synthesis, and metabolism. We hypothesized that rapidly proliferating cancer cells would become preferentially labeled with deuterium due to high metabolic activity, thus allowing imaging of biosynthetically labeled metabolites within tumorsin vivo. We initiated systemic D2O labeling in two established tumor xenograft models, HT-29 and MiaPaCa-2 and imaged mice by deuterium magnetic resonance spectroscopic imaging (dMRSI). After 14 days of tumor growth and 7 days ofin vivolabeling, a clear contrast was demonstrated between the xenograft and the contralateral control limb in both models. The origin of the contrast was traced to an aliphatic peak at 1.8 ppm, which was identified byex vivoNMR analysis to originate from cholesterol and cholesterol esters. Cholesterol is important for tumor cell proliferation, signaling, and malignant transformation, while current methods to monitor cholesterol synthesis and accumulation are limited. This deuterated water labeling-imaging approach could complement current cancer imaging techniques, allowing not only imaging of uptake but also synthesis of cholesterol to elucidate effects on tumor cholesterol metabolismin vivo.