The power of FDG-PET to detect treatment effects is increased by glucose correction using a Michaelis constant

We compared Ki, MRgluc (both with and without glucose normalization), and M R gluc max as FDG-PET measures of treatment-induced changes in tumor glucose uptake independent of any systemic changes in blood glucose caused either by natural variation or by side effects of drug action. Data from three xenograft models with independent evidence of altered tumor cell glucose uptake were studied and generalized with statistical simulations and mathematical derivations. To obtain representative simulation parameters, we studied the distributions of Ki from FDG-PET scans and blood [glucose] values in 66 cohorts of mice (665 individual mice). Treatment effects were simulated by varying M R gluc max and back-calculating the mean Ki under the Michaelis-Menten model with KM？=？130？mg/dL. This was repeated to represent cases of low, average, and high variability in Ki (at a given glucose level) observed among the 66 PET cohorts.There was excellent agreement between derivations, simulations, and experiments. Even modestly different (20%) blood glucose levels caused Ki and especially MRgluc to become unreliable through false positive results while M R gluc max remained unbiased. The greatest benefit occurred when Ki measurements (at a given glucose level) had low variability. Even when the power benefit was negligible, the use of M R gluc max carried no statistical penalty. Congruent with theory and simulations, M R gluc max showed in our experiments an average 21% statistical power improvement with respect to MRgluc and 10% with respect to Ki (approximately 20% savings in sample size). The results were robust in the face of imprecise blood glucose measurements and KM values.When evaluating the direct effects of treatment on tumor tissue with FDG-PET, employing a Michaelis-Menten glucose correction factor gives the most statistically powerful results. The well-known alternative ‘correction’, multiplying Ki by blood glucose (or normal