Summary:Positron emission tomography studies with the opiate antagonist [18F]cyclofoxy ([18F]CF) were per formed in baboons. Bolus injection studies demonstrated initial uptake dependent on blood flow. The late uptake showed highest binding in caudate nuclei, amygdala, thal amus, and brainstem and the least accumulation in cere bellum. By 60 min postinjection, regional brain radioac tivity cleared at the same rate as metabolite-corrected plasma, i.e., transient equilibrium was achieved. Com partmental modeling methods were applied to time activity curves from brain and metabolite-corrected plasma. Individual rate constants were estimated with poor precision. The model estimate of the total volume of distribution (VT), representing the ratio of tissue radioac tivity to metabolite-corrected plasma at equilibrium, was reliably determined. The apparent volume of distribution Va significantly overestimated V T and produced artifi cially high image contrast. These differences were pre dicted by compartment model theory and were caused by a plasma clearance rate that was close to the slowest tissue clearance rate. To develop a simple method to mea sure V T' an infusion protocol consisting of bolus plus continuous infusion (B/I) of CF was designed and applied in a separate set of studies. The Va values from the B/I studies agreed with the V T values from both B/I and bolus studies. This infusion approach can produce accurate re ceptor measurements and has the potential to shorten scan time and simplify the acquisition and processing of scan and blood data.

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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Positron emission tomography with simultaneous electroencephalographic monitoring was performed with [18F]fluorodeoxyglucose in 20 patients with complex partial seizures who had normal computed tomographic scans. Seven patients had only unilateral epileptiform discharges on the electroencephalogram, 3 had predominantly unilateral discharges, and 10 had nonlocalized epileptiform abnormalities. Positron emission tomography showed a hypometabolic lesion in 16 of the 20 patients. Pathological changes in the hypometabolic region were found in postoperative specimens in 4 of 5 patients studied. Positron emission tomography was unaffected by the seizure frequency, state of alertness, or number of spike discharges during the scan. There was a tendency for patients to have higher overall metabolic rates when taking less medication. Seizures occurring during [18F]fluorodeoxyglucose uptake in 3 patients produced a hypermetabolic area at the interictal hypometabolic focus. Positron emission tomography sometimes showed more widespread hypometabolism than suspected on the basis of the scalp-recorded electroencephalogram. The frontal lobe showed a greater degree of hypometabolism than the temporal lobe in 3 patients. Focal lesions may be identified by positron emission tomography even if the electroencephalographic abnormality is not well localized.

Arachidonic acid (AA) is an important second messenger involved in signal transduction mediated by phospholipase A2. The goal of this study was to establish an in vivo quantitative method to examine the role of AA in this signaling process in the human brain. A simple irreversible uptake model was derived from rat studies and modified for positron emission tomography (PET) to quantify the incorporation rate K* of [11C]AA into brain. Dynamic 60-minute three-dimensional scans and arterial input functions were acquired in 8 young healthy adults studied at rest. Brain radioactivity was corrected for uptake of the metabolite [11C]CO2. K* and cerebral blood volume (Vb) were estimated pixel-by-pixel and were calculated in regions of interest. K* equaled 5.6+/-1.2 and 2.6+/-0.5 microL x min(-1) x mL(-1) in gray and white matter, respectively. K* and Vb values were found to be unchanged with data analysis periods from 20 to 60 minutes. Thus, PET can be used to obtain quantitative images of the incorporation rate K* of [11C]AA in the human brain. As brain incorporation of labeled AA has been shown in awake rats to be increased by pharmacological activation associated with phospholipase A2-signaling, PET and [11C]AA may be useful to measure signal transduction in the human brain.