E. Stephen Garnett

Striatal dopamine distribution in Parkinsonian patients during life

Eleven neuropsychologically normal Parkinsonian patients were studied with [18F]6-fluoro-L-dopa and positron tomography. In all of the patients dopaminergic activity was reduced in the putamen on the side opposite to the major motor signs. The reduction was similar in tremulous and rigid patients. In contrast dopaminergic activity was normal in the caudate nuclei. It is argued that the putamen is mainly involved in the regulation of movement while the caudate nuclei assume a role in cognitive processes.

Redistribution of Myocardial Blood Flow With Topical Nitroglycerin in Patients With Coronary Artery Disease

BACKGROUND Unlike nonselective coronary vasodilators, nitroglycerin (GTN) is said to exert its primary vasodilatory effect on epicardial conductance vessels. Thus, in experimental models of coronary occlusion GTN appears to preferentially direct blood flow to poststenotic zones of ischemia. This phenomenon has, to date, not been tested in humans. Using positron emission tomography we examined the effect of transdermal GTN on global and regional myocardial perfusion in patients with angiographically proven coronary artery disease. METHODS AND RESULTS Myocardial perfusion with [13N]ammonia was estimated from dynamic time-activity curves at baseline and 3 hours following application of either a 0.4 mg/h GTN skin patch (n = 10) or a placebo patch (n = 10) in a double-blind parallel design. From resliced cross-sectional images, regional flow, expressed as [13N]ammonia retention, was estimated from 216 myocardial sectors. Ischemia was defined as a significant reduction (> 2 SDs from average counts/pixel in maximally perfused zones) in [13N]ammonia retention within 10 contiguous myocardial sectors coupled with an increase or no change in counts derived from [18F]fluorodeoxyglucose. There was no change in global myocardial blood flow as expressed by [13N]ammonia retention following either placebo (0.61 +/- 0.14 to 0.62 +/- 0.12 min-1) or GTN (0.75 +/- 0.22 to 0.74 +/- 0.19 min-1). Conversely, there was a significant increase in the proportion of blood flow to the ischemic zones with GTN (73.9 +/- 12.6% to 94.9 +/- 17.8%; P < .05). No change in the distribution of blood flow to either ischemic or nonischemic zones was observed with placebo. A slight but insignificant decrease in [13N]ammonia retention in nonischemic zones was observed with GTN (1.01 +/- 0.31 to 0.93 +/- 0.26 min-1). CONCLUSIONS This study suggests that under resting conditions topical GTN alters myocardial perfusion by preferentially increasing flow to areas of reduced perfusion with little or no change in global myocardial perfusion in patients whose angina is responsive to GTN.

The Distribution and Kinetics of [18F]6-Fluoro-3-O-methyl-L-dopa in the Human Brain

The analysis of positron tomographic studies of 3,4-dihydroxyphenylethylamine (dopamine) metabolism in which [18F]6-fluoro-l-3,4-dihydroxyphenylalanine (F-dopa) is used as a tracer is confounded by the presence of [18F]6-fluoro-3-O-methyl-l-3,4-dihydroxyphenylalanine (OMFD). This labeled molecule, formed by the action of peripheral cathechol-O-methyltransferase on F-dopa, crosses the blood–brain barrier and contributes to the radioactivity measured by the tomograph. Corrections for this radioactivity in the brain have been proposed. They rely upon the assumption that regional variations in the handling of this molecule by the brain are negligible. Although this assumption is pivotal for the proper quantification of dopamine metabolism using F-dopa, the distribution and kinetics of OMFD have never been studied in humans. We present results in humans that show that there is little selective regional 18F accumulation in the brain, that the distribution volume of OMFD is close to unity, and that a single, reversible compartment is adequate to model the measured time course of radioactivity after an OMFD injection. Analysis of plasma samples for labeled metabolites showed that more than 95% of the radioactivity was associated with OMFD at all times. Our results for OMFD kinetics are in accord with published results obtained in nonhuman primates and for the bidirectional transport of large neutral amino acids across the blood-brain barrier measured using a synthetic amino acid. However, our results also indicate that there are small but significant differences in OMFD kinetics in different parts of the brain that may prevent inferences about the handling of OMFD in one part of the brain from being extended to other parts of the brain.

Regional cerebral glucose metabolism of newborn infants measured by positron emission tomography.

The new diagnostic technique, positron emission tomography with 18F‐2‐fluoro‐2‐deoxy‐D‐glucose (18FDG), was used to measure regional cerebral glucose metabolism in five newborn infants with demonstrated structural abnormalities of the brain. 18FDG was synthesized, diluted in normal saline and injected intravenously. After one hour, tomographic slices of the brain were obtained, the level of the slices being defined relative to the cerebral ventricles.

Electrochemical monofluorination of pyridine: synthesis of 2-fluoropyridine at a platinum anode☆

2-Fluoropyridine has been synthesized in 22% yield by electrochemical fluorination of pyridine at a platinum anode at 2.5 V vs Ag/Ag+ (0.1 M) and with 0.5 M tetramethylammonium dihydrogen trifluoride (Me4NF·2HF) in dry acetonitrile as supporting electrolyte and fluoride source. At lower ME4NF·2HF concentrations and at lower applied potentials both yield and reaction rate are decreased whereas at higher potentials the supporting electrolyte/solvent system decomposes. The choice and purity of supporting electrolyte is an important factor in determining the product distribution and yield. The relatively low fluoride concentration allows use of a glass cell.

Can Nitrogen-13 Ammonia Kinetic Modeling Define Myocardial Viability Independent of Fluorine-18 Fluorodeoxyglucose?

OBJECTIVES The hypothesis of this study was that evaluation of myocardial flow and metabolism using nitrogen-13 (N-13) ammonia kinetic modeling with dynamic positron emission tomographic (PET) imaging could identify regions of myocardial scar and viable myocardium as defined by fluorine-18 fluorodeoxyglucose (F-18 FDG) PET. BACKGROUND Uptake of most perfusion tracers depends on both perfusion and metabolic retention in tissue. This characteristic has limited their ability to differentiate myocardial scar from viable tissue. The kinetic modeling of N-13 ammonia permits quantification of blood flow and separation of the metabolic component of its uptake, which may permit differentiation of scar from viable tissue. METHODS Sixteen patients, > 3 months after myocardial infarction, underwent dynamic N-13 ammonia and F-18 FDG PET imaging. Regions of reduced and normal perfusion were defined on static N-13 ammonia images. Patients were classified into two groups (group I [ischemic viable], n = 6; group II [scar], n = 10) on the basis of percent of maximal F-18 FDG uptake in hypoperfused segments. Nitrogen-13 ammonia kinetic modeling was applied to dynamic PET data, and rate constants were determined. Flow was defined by K1; volume of distribution (VD = K1/k2) of N-13 ammonia was used as an indirect indication of metabolic retention. RESULTS Fluorine-18 FDG uptake was reduced in patients with scar compared with normal patients with ischemic viable zones (ischemic viable 93 +/- 27% [mean +/- SD]; scar 37 +/- 16%, p < or = 0.01). Using N-13 ammonia kinetic modeling, flow and VD were reduced in the hypoperfused regions of patients with scar (ischemic viable flow: 0.65 +/- 0.20 ml/min per g, scar: 0.36 +/- 0.16 ml/min per g, p < or = 0.01; VD: 3.9 +/- 1.3 and 2.0 +/- 1.07 ml/g, respectively, p < or = 0.01). For detection of viable myocardium in these patients, the sensitivity and specificity were 100% and 80% for N-13 ammonia PET flow > 0.45 ml/min per g; 100% and 70% for VD > 2.0 ml/g; and 100% and 90% for both flow > 0.45 ml/min per g and VD > 2.0 ml/g, respectively. The positive and negative predictive values for the latter approach were 86% and 100%, respectively. CONCLUSIONS In this cohort, patients having regions with flow < or = 0.45 ml/min per g or VD < or = 2.0 ml/g had scar. Viable myocardium had both flow > 0.45 ml/min per g and VD > 2.0 ml/g. Nitrogen-13 ammonia kinetic modeling permits determination of blood flow and metabolic integrity in patients with previous myocardial infarction and can help differentiate between scar and ischemic but viable myocardium.

Synthesis of [18F]XeF2, a novel agent for the preparation of 18F-radiopharmaceuticals

[18F]XeF2 was synthesised by isotopic exchange between XeF2 and anhydrous reactor-produced [18F]HF, [18F]SiF4, and [18F]AsF5 with a radiochemical yield of 30%; [18F]XeF2 may facilitate the direct radiofluorination of organic tracer molecules for positron emission tomography.

THE ASSESSMENT OF ANEMIA IN SMALL PREMATURE INFANTS

Changes in hemoglobin concentration in premature infants are difficult to interpret because of variations in blood volume and blood loss. We have determined circulating red cell volume (RCV) and erythrocyte survival by Cr51 red cell labelling using capillary techniques. In six infants whose weights varied from 680-1, 320 g, RCV was 29.5 ± 6.4 ml/kg.In these babies, blood lost for laboratory tests during the first three weeks of life averaged 0.81 ml/kg/day. In addition all materials contaminated by blood (sponges, syringes, etc.) were collected and the content of Cr51 labelled cells was determined. A correlation was found (r=0.60; p<0.01) between the amount of blood taken for tests and that in contaminated materials (0.08 ml/kg/day).The assessment of erythrocyte survival and of changes in hemoglobin concentration demands quantitation of blood lost through sampling. This, together with direct measurement of RCV permits a more complete evaluation of anemia in small premature infants.

Display of Hemispheric Local Metabolic Rates from Human Brain

Positron tomography, a technique that employs the concepts of computerized tomography in combination with specific molecules labelled with positron emitters, is now making possible the direct regional measurement of blood flow and energy requirements or the mapping of the distribution of molecules such as neurotransmitters and the drugs that affect the central nervous system. This technique allows accurate recovery of the distribution of the labelled molecules in thicknesses of grey and white matter in cross sections through the brain. Although sixteen to twenty different levels are routinely examined during a typical study, the data in each tomographic section is usually considered in isolation. A major problem with this approach is that it does not consider the major subdivisions of the brain, the various lobes and gyri, in their entirety. These structures often overlap many tomographic sections, and are not always easily traceable from section to section. We describe an approach that maps the distribution of radioactivity, and hence of the process being studied, over the whole of the cortical mantle from a knowledge of the distribution in the transaxial sections. Our approach allows a more accurate localization of defects in the brain, and a more accurate quantification of the extent of the deficit in the cortical mantle.