The enzymatic basis of the biodistribution of FDG: Implications for tumor imaging

In this paper, the authors have begun to evaluate the following hypothesis: the differential concentration (conc) of fluorodeoxyglucose (FDG) between normal and malignant tissues in vivo, and thus the likelihood of ''hot spot'' /sup 18/FDG tumor imaging, can be predicted on the basis of their relative hexokinase (H)-to-glucose-6-phosphatase (P) ratios. The authors' assumption is that the greater H relative to P, the greater the intracellular conc of FDG-6-phosphate (FDGP) and therefore the greater the tissue conc of total /sup 18/F following /sup 18/FDG administration. They determined tissue conc of total /sup 14/C and of /sup 14/C-FDG and -FDGP. They determined tissue conc of total /sup 14/C and of /sup 14/C-FDG and -FDGP 45' after iv injectino of 5 ..mu..Ci /sup 14/C(U)-FDG (343 ..mu..Ci/..mu..mol) into normal C57Br mice. Tissue H and P were determined by measuring colorimetrically the time-dependent glucose utilization and phosphate production, respectively. Consistent with this hypothesis, significant positive correlations were found between total /sup 14/C conc and the H-to-P ratio (r=.99, rho<.001), between the /sup 14/C-FDGP-to-/sup 14/C-FDG ratio and the H-to-P ratio (r=.91, rho<.0025), and between total /sup 14/C conc and the /sup 14/C-FDGP-to-/sup 14/C-FDG ratio (r=.79, rho<.025). This last correlation provides the basis for a simple methodmore » (which the authors are currently testing) for predicting total /sup 18/F conc in tumor and in contiguous tissue by measuring its FDGP-to-FDG equilibrium ratio in vitro. Thus, besides explaining the biochemical basis of tumor localization of a potentially important diagnostic agent, the authors have devised a simple method to predict its clinical efficacy.« less