Metabolic trapping as a principle of oradiopharmaceutical design: some factors resposible for the biodistribution of [18F] 2-deoxy-2-fluoro-D-glucose.

Abstract

Initially, [18F]2-deoxy-2-fluoro-D-glucose (F-18-DG) distributes to the kidneys, heart, brain, lungs, and liver of the mouse, and clears rapidly from all except the heart and, to a much lesser extent, the brain. The heart and brain showed the highest rates of phosphorylation both in vivo and in vitro. No detectable glucose-6-phosphatase activity was present in these organs when hexokinase activity was high and at pH 6.5. The rank order for hexokinase activity, measured in vitro, was brain > heart ≃ kidney > lung > liver, whereas glucose-6-phosphatase activity was found only in the liver and to a lesser extent in the kidney, at pH 6.5. The rate of appearance of F-18-DG-6 phosphate (F-18-DG-6-P) in vivo was significantly slower in the lungs, liver, and kidneys than in the heart and brain, and represented a small proportion of the initial radioactivity. The F-18-DG that clears from the organs is excreted into the urine mostly unchanged, apparently due to the lack of tubular resorption. The rapid excretion of F-18-DG from liver, lungs and kidneys, and the retention by the heart and brain, is the result of metabolic trapping within certain organs and is reflective of glucose utilization. These results may contribute to the clinical utility of F-18-DG by providing a basis for metabolic studies in vivo. Metabolic trapping can be considered as a principle in the design of radiopharmaceuticals as metabolic probes for function or tumor location.

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