Determination of Kinetic Rate Constants for 2-[¹⁸F]fluoro-2-deoxy-d-glucose and Partition Coefficient of Water in Conscious Macaques and Alterations in Aging or Anesthesia Examined on Parametric Images with an Anatomic Standardization Technique

Abstract

Summary: Kinetic rate constants for 2-[18 F]fluoro-2-deoxy-D-glucose (FDG) and the tissue-blood partition coefficient of water were determined using dynamic positron emission tomography in conscious macaques, and alterations in these parameters in aging or anesthesia were also examined. The parameters were estimated on a pixel-by-pixel basis using an anatomic standardization technique; group differences were then examined on the parametric images from the young, aged, and anesthesia groups. For the conscious condition, seven young and seven aged male rhesus macaques were used; six young male rhesus macaques were used for the isoflurane anesthesia condition. H 2 15O and FDG were used as tracers. The kinetic parameters were estimated by a nonlinear least-square fitting procedure with compartment models including terms for the cerebral blood volume (CBV) and time delay of the input function. Cerebral blood flow (CBF) and cerebral metabolic rate of glucose (CMRglc) were also calculated from the estimated parameters. In the aged group, glucose phosphorylation was decreased more than glucose transport, and the occipital cortex was the most affected region where reduction in CBV, CMRglc, and CBF were also observed. In the anesthesia group, glucose transport was decreased; however, glucose phosphorylation was not affected except for the occipital pole. The occipital cortex was also the most affected region. The tissueblood partition coefficient of water was decreased globally. Key Words: Compartment analysis-Anatomic standardization-Cerebral glucose transport-Cerebral glucose phosphorylation-Tissue-blood partition coefficient. H 215 O and 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG) are used for positron emission tomography (PET) to measure cerebral blood flow (CBF) and the cerebral metabolic rate of glucose (CMRglc). These tracers have been widely used in humans, and several studies have also been performed in macaques. Because glucose is the primary energy source for the mammalian brain and blood flow is continually adjusted to meet dynamic alterations in metabolic demand, CMRglc and CBF are useful and important parameters when investigating brain function. PET allows measurement of these parameters in various physiologic and pathologic states and also allows investigation of dynamic alterations in living subjects. In calculating CMRglc and CBF from PET data with a conventional autoradiographic method, kinetic rate constants of FDG and the tissue-blood partition coefficient of water are required. Though these constants for human PET studies are well established, those for animal PET studies are not. Therefore, in previous studies, the constants for humans were alternatively used for macaques. In the present study, these constants were determined in conscious macaques using dynamic PET.Dynamic PET also allows noninvasive investigation of the initial steps of metabolism with tracer kinetics modeling. Several dynamic PET studies in Alzheimer's disease (AD) demonstrated alterations in glucose transport, as well as phosphorylat...

Effects of neonatal amygdala or hippocampus lesions on resting brain metabolism in the macaque monkey: A microPET imaging study

“…Since all animals underwent the same protocol, anesthesia per se should not induce group differences in glucose metabolism. Moreover, since isoflurane typically reduces cerebral metabolism relative to the non-anesthetized state (Noda et al, 2003, Shimoji et al, 2004, the differences between groups reported here may be underestimates of the actual differences.…”

“…Since all animals underwent the same protocol, anesthesia per se should not induce group differences in glucose metabolism. Moreover, since isoflurane typically reduces cerebral metabolism relative to the non-anesthetized state (Noda et al, 2003, Shimoji et al, 2004, the differences between groups reported here may be underestimates of the actual differences.An intravenous catheter was placed in the right cephalic vein for acquiring a blood sample, infusion of [ 18 F]FDG and delivery of fluids (lactated Ringer's solution). Opthalmic ointment was again placed in the animals' eyes to prevent drying.…”

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“…34 In summary, CBF and cerebral blood volume (CBV) are typically decreased by anaesthesia produced by propofol and increased by ketamine and isoflurane/halothane in animals used for PET neuroimaging. 30 12,20,45,46 These changes are particularly important in quantitative kinetic analysis of brain glucose metabolism, although reduced neural activity caused by anaesthesia may also affect the outcome of PET studies on new drugs such as CNS stimulants. Anaesthetics can also affect blood levels of glucose and lipids that can indirectly affect brain metabolism.…”

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