A method has been developed to measure local glucose consumption in the various structures of the brain in man with three-dimensional resolution. [18F]-2-deoxy-2-fluoro-D-glucose is used as a tracer for the exchange of glucose between plasma and brain and its phosphorylation by hexokinase in the tissue. A mathematical model and derived operational equation are used which enable local cerebral glucose consumption to be calculated in terms of the following measurable variables. An intravenous bolus of [18F]-2-deoxy-2-fluoro-D-glucose is given and the arterial specific activity monitored for a predetermined period of from 30 to 120 minutes. Starting at 30 minutes, the activity in a series of sections through the brain is determined with three-dimensional resolution by an emission tomographic scanner. The method was used to measure local cerebral glucose consumption in two normal volunteers. The values in gray matter structures range from 5.79 mg/100 g per minute in the cerebellar cortex to 10.27 in the visual cortex, whereas, in white matter structures, the values range from 3.64 mg/100 g per minute in the corpus callosum to 4.22 in the occipital lobe. Average values for gray matter, white matter, and whole brain metabolic rates, calculated as a weighted average based on the approximate volume of each structure, are 8.05, 3.80, and 5.90 mg/100 g per minute, respectively. The value of 5.9 mg/100 g per minute compares favorably with values previously reported.

Five patients who had undergone radiation therapy for cerebral tumors and whose conditions were deteriorating were examined by means of positron emission tomography (PET) with [18F] fluorodeoxyglucose. All five cases had similar clinical and computed tomographic findings. Using the PET technique the two cases of radiation necrosis were distinguished from the three recurrent tumors. In the two cases of radiation necrosis the rate of glucose utilization in the lesion was markedly reduced compared with the normal brain parenchyma. In the recurrent gliomas, however, the glucose metabolic rate was elevated. All five diagnoses were confirmed by biopsy or autopsy.

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The 2-[18F]fluoro-2-deoxy-D-glucose technique was used to measure regional cerebral glucose utilization by human subjects during functional activation. Normal male volunteers subjected to one or more sensory stimuli (tactile, visual, or auditory) exhibited focal increases in glucose metabolism in response to the stimulus. Unilateral visual hemifield stimulation caused the contralateral striate cortex to become more metabolically active than the striate cortex ipsilateral to the stimulated hemifield. Similarly, stroking the fingers and hand of one arm with brush produced an increase in metabolism in the contralateral postcentral gyrus, compared with the homologous ipsilateral region. The auditory stimulus, which consisted of a monaurally presented factual story caused an increase in glucose metabolism in the auditory cortex in the hemisphere contralateral to the stimulated ear. These results demonstrate that the technique is capable of providing functional maps in vivo related to both body region and submodality of sensory information in the human brain.

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Because CNS neuroleptic concentration cannot be directly measured in patients, the relation between clinical response and extent of dopamine receptor blockade is unknown. This relationship is critical in ascertaining whether nonresponse to neuroleptics is the result merely of inadequate CNS drug levels or of more basic biological differences in pathophysiology. Using [18F]N-methylspiroperidol and positron emission tomography, the authors assessed dopamine receptor occupancy in 10 schizophrenic patients before and after treatment with haloperidol. Responders and nonresponders had virtually identical indices of [18F]N-methylspiroperidol uptake after treatment, indicating that failure to respond clinically was not a function of neuroleptic uptake or binding in the CNS.

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