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Purpose: The aim of this study is to compare glucose metabolism and hypoxia in four different tumor types using positron emission tomography (PET).18 F-labeled fluorodeoxyglucose (FDG) evaluates energy metabolism, whereas the uptake of 18 F-labeled fluoromisonidazole (FMISO) is proportional to tissue hypoxia. Although acute hypoxia results in accelerated glycolysis, cellular metabolism is slowed in chronic hypoxia, prompting us to look for discordance between FMISO and FDG uptake.Experimental Design: Forty-nine patients (26 with head and neck cancer, 11 with soft tissue sarcoma, 7 with breast cancer, and 5 with glioblastoma multiforme) who had both FMISO and FDG PET scans as part of research protocols through February 2003 were included in this study. The maximum standardized uptake value was used to depict FDG uptake, and hypoxic volume and maximum tissue: blood ratio were used to quantify hypoxia. Pixel-by-pixel correlation of radiotracer uptake was performed on coregistered images for each corresponding tumor plane.Results: Hypoxia was detected in all four patient groups. The mean correlation coefficients between FMISO and FDG uptake were 0.62 for head and neck cancer, 0.47 for breast cancer, 0.38 for glioblastoma multiforme, and 0.32 for soft tissue sarcoma. The correlation between the overall tumor maximum standardized uptake value for FDG and hypoxic volume was small (Spearman r ‫؍‬ 0.24), with highly significant differences among the different tumor types (P < 0.005).Conclusions: Hypoxia is a general factor affecting glucose metabolism; however, some hypoxic tumors can have modest glucose metabolism, whereas some highly metabolic tumors are not hypoxic, showing discordance in tracer uptake that can be tumor type specific.

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Animal and histopathological studies of human brain support a role for P-glycoprotein (P-gp) in clearance of cerebral β-amyloid (Aβ) across the blood brain barrier (BBB). We tested the hypothesis that BBB P-gp activity is diminished in Alzheimer’s disease (AD) by accounting for AD-related reduction in regional cerebral blood flow (rCBF). Methods We compared P-gp activity in mild AD patients (n=9) and cognitively normal, age-matched controls (n=9) using positron emission tomography (PET) with a labeled P-gp substrate, [11C]-verapamil, and [15O]-water to measure rCBF. BBB P-gp activity was expressed as the [11C]-verapamil radioactivity extraction ratio (ER={[11C]-verapamil brain distributional clearance, K1}/rCBF). Results Compared to controls, BBB P-gp activity was significantly lower in the parietotemporal, frontal, posterior cingulate cortices and hippocampus of mild AD subjects. Conclusion BBB P-gp activity in brain regions affected by AD is reduced and is independent of rCBF. This study improves on prior work by eliminating the confounding effect that reduced rCBF has on assessment of BBB P-gp activity and suggests that impaired P-gp activity may contribute to cerebral Aβ accumulation in AD. P-gp induction/activation to increase cerebral Aβ clearance could constitute a novel preventive or therapeutic strategy for AD.