Abstract
A deuterium NMR spectroscopic method to determine relative tumor blood flow (TBF) by measuring the increase in tumor HOD concentration after intravenous injection of 100 microliters D2O (0.9% NaCl) is presented. An integration approach analogous to that validated for positron emission tomographic measurement of cerebral blood flow was implemented. Computer simulations indicated that integration from 30 to 120 s minimizes the sensitivity of the uptake integral to the shape of the arterial input function, which cannot be assessed in each mouse, while maintaining both a nearly linear relationship between TBF and the integral and high NMR signal-to-noise. A strong positive linear correlation was observed between the uptake integral and TBF measured by D2O clearance in both untreated tumors (n = 19; P less than 0.001) and tumors after hyperthermia (n = 16; P less than 0.001). This method can measure relative TBF in tumors with heterogeneous blood flow and is ideally suited to concurrent or interleaved measurement of TBF and metabolism via multinuclear NMR spectroscopy.
Published Version
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