Cerebral Glucose Metabolism as a Function of Age in Man: Influence of the Rate Constants in the Fluorodeoxyglucose Method

Abstract

Summary: Measurement of the local cerebral metabolic rate of glucose (LCMRGlc) with the fluorodeoxyglucose (FDG) method requires the utilization of appropriate val ues for the rate constants of the transport and phosphor ylation processes, We measured these rate constants as a function of age to determine whether a decline in LCMRGlc as a function of age, in prior studies with the The deoxyglucose method originally developed by Sokoloff et aL (1977) and applied to humans by Reivich et aL (1979), Phelps et aL (1979), andHuang et aL (1980) provides a measurement of the local cerebral metabolic rate of glucose (LCMRGlc). The Sokoloff model, as modified by Phelps et aL (1979) and Huang et aL (1980), requires the rate constants kl* and k2* for forward and reverse membrane transport of fluorodeoxyglucose (FDG), and k3* and k4* for phosphorylation of FDG and dephosphory lation of FDG-6-P04' Prior investigations have demonstrated that in altered states of metabolism, values obtained for LCMRGlc can be in error if inappropriate rate constants are used (Hawkins et aI., 1981; Huang et aI., 1981 may occur, although the most significant errors occur in hypo metabolic states.Several investigators have demonstrated a de cline in the rate of human cerebral glucose metabo lism (CMRGlc) as a function of age, using inert gas clearance methods for measuring flow and cal culating glucose metabolism as the product of cere bral blood flow (CBF) and cerebral A-V glucose difference (Dastur et aI., 1963; Gottstein et aI., 1971;Gottstein and Held, 1979). Kuhl et aL (1982) made similar observations with positron tomogra phy and the FDG method. We evaluated the rate constants in order to determine whether the ob served decline in metabolism actually reflects a change in rate constants and to search for any selective alteration in the transport or phosphoryla tion processes as a function of age. MATERIALS AND METHODSEight neurologically normal volunteers, 7 males and 1 female. were studied. Their ages were 18, 21, 28, and 32 (group I) and 53, 58, 63, and 68 (group 11).All subjects were given 10 mCi [18F]FDG i.v. and scanned with a N euroECA T positron tomograph (image resolution 11.7 x 11. 7 mm FWHM in plane and 13. 4 mm axially, in the operating mode employed in this study)

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