Stable Water Isotope Labeling for Imaging of Rapidly Proliferating Cells

Division Of Basic Sciences - Nci

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Abstract

Water is a substrate in many biochemical reactions. As a result, deuterated water (D2O) has been used to study cell kinetics, protein synthesis, and metabolism. We hypothesized that systemic administration of D2O would result in preferential biosynthetic labeling of tumor metabolites allowing their in vivo detection by deuterium magnetic resonance imaging (dMRI). We tested this approach in two established tumor xenograft models. Following 14 days of tumor growth and 7 days of labeling, a clear contrast was demonstrated between the xenografts and the contralateral control limbs. The origin of the contrast was traced to an aliphatic peak at 1.8 ppm, which was identified by ex vivo NMR to originate from cholesterol and cholesterol esters. Cholesterol metabolism is important for tumor cell proliferation, signaling, and malignant transformation, while current methods to monitor cholesterol synthesis and accumulation are limited. Our D2O labeling-dMRI approach enables in vivo evaluation of tumor cholesterol metabolism.