Quantitative Assessment of Heterogeneity in Tumor Metabolism Using FDG-PET

Purpose: [F-18]-fluorodeoxyglucose-positron emission tomography (FDG-PET) images are usually quantitatively analyzed in whole-tumor volumes of interest. Also parameters determined with dynamic PET acquisitions, such as the Patlak glucose metabolic rate (MRg1c) and pharmacokinetic rate constants of two-tissue compartment modeling, are most often derived per lesion. We propose segmentation of tumors to determine tumor heterogeneity, potentially useful for dose-painting in radiotherapy and elucidating mechanisms of FDG uptake. Methods and Materials: In 41 patients with 104 lesions, dynamic FDG-PET was performed. On MRglc images, tumors were segmented in quartiles of background subtracted maximum MRglc (0%-25%, 25%-50%, 50%-75%, and 75%-100%). Pharmacokinetic analysis was performed using an irreversible two-tissue compartment model in the three segments with highest MRglc to determine the rate constants of FDG metabolism. Results: From the highest to the lowest quartile, significant decreases of uptake (K-1), washout (k(2)), and phosphorylation (k(3)) rate constants were seen with significant increases in tissue blood volume fraction (V-b). Conclusions: Tumor regions with highest MRglc are characterized by high cellular uptake and phosphorylation rate constants with relatively low blood volume fractions. In regions with less metabolic activity, the blood volume fraction increases and cellular uptake, washout, and phosphorylation rate constants decrease. These results support the hypothesis that regional tumor glucose phosphorylation rate is not dependent on the transport of nutrients (i.e., FDG) to the tumor. (C) 2012 Elsevier Inc.