TRANSPORT OF D-GLUCOSE AND 2-FLUORODEOXYGLUCOSE ACROSS THE BLOOD-BRAIN-BARRIER IN HUMANS

The deoxyglucose method for calculation of regional cerebral glucose m etabolism by PET using F-18-2-fluoro-2-deoxy-d-glucose (FDG) requires knowledge of the lumped constant, which corrects for differences in th e blood-brain barrier (BBB) transport and phosphorylation of FDG and g lucose. The BBB transport rates of FDG and glucose have not previously been determined in humans, In the present study these transport rates were measured with the intravenous double-indicator method in 24 heal thy subjects during normoglycemia (5.2 +/- 0.7 mM). Nine subjects were restudied during moderate hypoglycemia (3.4 +/- 0.4 mM) and five subj ects were studied once during hyperglycemia (15.0 +/- 0.7 mM). The glo bal ratio between the unidirectional clearances of FDG and glucose (K- 1/K-1) was similar in normoglycemia (1.48 +/- 0.22), moderate hypogly cemia (1.41 +/- 0.23), and hyperglycemia (1.44 +/- 0.20). This ratio i s comparable to what has been obtained in rats. We argue that the glob al ratio is constant throughout the brain and may be applied for the r egional determination of LC, We also determined the transport paramete rs of the two hexoses from brain back to blood and, assuming symmetric al transport across the BBB, we found evidence of a larger initial dis tribution volume of FDG in brain (0.329 +/- 0.236) as compared with th at of glucose (0.162 +/- 0.098, p < 0.005). The difference can be expl ained by the very short experimental time, in which FDG may distribute both intra- and extracellularly, whereas glucose remains in a volume comparable to the interstitial fluid of the brain.