E.S. Garnett

Increased frontal and reduced parietal glucose metabolism in acute untreated schizophrenia

Frontal and parietal lobe metabolism was measured by [18F] fluorodeoxyglucose positron emission tomography in 8 never-medicated DSM-III schizophrenic patients and in 10 control subjects. Patients were in a psychotic episode at the time of this scan. Seven of eight had been ill less than 2 years and had only mild neurocognitive impairment. Frontal lobe glucose metabolism was significantly greater in schizophrenic patients than in controls. This finding differs from that of hypofrontality reported in chronic patients previously treated with neuroleptics. Relative glucose metabolism in the interior parietal lobe was significantly lower in schizophrenic patients than in controls. The frontal/parietal ratios were significantly greater in patients than in controls.

Cerebral Metabolism of 6–[18F]Fluoro‐l‐3,4‐Dihydroxyphenylalanine in the Primate

Abstract: The tracers 6‐[18F]fluoro‐1‐3,4‐dihydroxyphenyl‐alanine (6–[18F]fluoro‐l‐DOPA) and 1‐[14C]DOPA were injected simultaneously into rhesus monkeys, and the time course of their metabolites was measured in the striatum and in the occipital and frontal cortices. In the striatum, 6‐[18F]fluoro‐L‐DOPA was metabolized to 6–[18F]fluorodo‐pamine, 3,4‐dihydroxy‐6–[18F]fluorophenylaceticacid, and 6–[18F]fluorohomovanillic acid. The metabolite pattern was qualitatively similar to that of 1‐[14C]DOPA. 6–[18F]Fluorodopamine was synthesized faster than [14C]do‐pamine. In the frontal cortex, the major metabolite was also 6–[18F]fluorodopamine or [14C]dopamine. In the occipital cortex, the major metabolite was 3‐O‐methyl‐6–[18F]fluoro‐L‐DOPA. On the basis of these data, the images obtained with 6–[l8F]fluoro‐l‐DOPA and positron emission tomography in humans can now be interpreted in neurochemical terms.

Reduced striatal glucose consumption and prolonged reaction time are early features in Huntington's disease ☆

Striatal glucose consumption was measured by positron emission tomography in 4 male patients, aged 16-27, suffering from Huntingtons disease and in 3 age-matched control subjects. Symptoms had been present for 3 years or less; they were mainly psychiatric. Two of the patients had no chorea although the time taken to initiate a movement was prolonged and there was some reduction in the speed at which movements could be executed. Caudate atrophy was absent or minimal by CAT scan yet striatal glucose consumption was markedly reduced in all of the patients. It is suggested that striatal glucose consumption is largely determined by the functional integrity of spiny neurones in the striatum.

Radiofluorination with 18F-labelled acetyl hypofluorite: [18F]L-6-fluorodopa

Abstract Acetyl hypofluorite labelled with 18F was produced in glacial acetic acid from [18F]F2 gas diluted with neon. L -3-Methoxy-4-hydroxyphenylalanine ethyl ester hydrochloride was reacted with the acetyl hypofluorite either in glacial acetic acid or in a mixture of glacial acetic and trifluoroacetic acids at room temperature for 20 min. After hydrolysis of the reaction products with 48% hydrobromic acid, L -[18F]6-fluorodopa (4%, EOB, radiochemical yield) was isolated by reverse phase high pressure liquid chromatography. Despite its low yield the method may be useful for the production of L -[18F]6-fluorodopa with which the dopamine rich regions of the brain can be demonstrated and with which dopamine metabolism can be measured by positron emission tomography.

The synthesis of [18F]Xenon difluoride from [18F]fluoride gas

Abstract A convenient procedure for the rapid synthesis of 18F labelled XeF2 was developed. Neon gas with 0.087 to 5% carrier fluorine was irradiated with 15 MeV deuterons to produce [18F]F2 with a yield of 17 mCi/μAh, EOB. It was, in turn, reacted with excess of xenon in a high pressure nickel vessel at 390°C for 40 min. The isolated reaction product was XeF2 exclusively. The production yield was 11 mCi/μAh at EOB and the specific activity was 450mCi/mmol. [18F]XeF2 has been shown to be a versatile intermediate for the syntheses of 18F-labelled radiopharmaceuticals, for example, [18F]2-fluoro-2-deoxy- D -glucose and L -[18F]6-fluorodopa.

Apomorphine effects on brain metabolism in neuroleptic-naive schizophrenic patients

Since neuroleptic treatment produces a significant increase in striatal metabolism relative to cortical metabolism, we wished to determine whether the dopamine agonist apomorphine (APO) might have the opposite effect, and whether it would discriminate schizophrenic patients from healthy controls. Eleven neuroleptic-naive schizophrenic patients (diagnosed according to DSM-III) and eight normal subjects were compared with respect to cerebral accumulation of 18F-fluorodeoxyglucose measured by positron emission tomography following APO, 0.75 mg/70 kg (weight adjusted), or saline. Relative striatal glucose metabolism decreased significantly after APO in schizophrenic patients but not in control subjects. Post hoc analysis of data in 12 other regions revealed that relative superior temporal metabolism decreased very slightly, but significantly, in schizophrenic patients but not in control subjects after APO, and that the posterior frontal region increased in control subjects but not in the patient group.

Measurement of absolute bone blood flow by positron emission tomography

A method of measuring bone blood flow has been developed using 18F sodium fluoride and positron emission tomography. The blood flow levels are in line with those obtained experimentally from microsphere embolisation. This investigative method could be applied to elucidate a number of clinical questions involving bone perfusion.

Performance Characteristics of the McMaster Positron Emission Tomograph

The McMaster Positron Emission Tomograph is an instrument designed for the high resolution cross sectional study of the human brain. The detector head comprises 160 Bismuth Germanate crystals, each coupled to a 12.7 mm photomultiplier tube, closely packed on a ring, 53.5 cm in diameter. The performance characteristics of the tomograph have been measured. The spatial resolution is 8 mm (FWHM) in the stationary mode. The slice thickness is 10 mm. The resolution element is a cube of side 8 mm. The sensitivity of the tomograph was measured using a cylindrical lucite phantom, 20 cm in diameter and 20 cm long, uniformly filled with a 1 ¿Ci/ml solution of 68Ga. The total number of coincident events is 18,200 cps for a 10 mm slice. Of these, 2200 cps are random coincidences. The instrument has been in clinical use for the past 18 months.