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Biomedical subjects

D F Wong

Publications and source records attributed to D F Wong.

At least 91 records · Page 5Linked to original sources
PubMed1988

Labeled plasma metabolites of L-methyl-hydrogen-3-methionine and L-methyl-carbon-14-methionine in the dog.

The validity of the mathematical models that attempt to describe positron emission tomography (PET) images produced with [11CH3] methionine in terms of rates of local cerebral protein synthesis has yet to be established. A major objection to current models is that the use of methionine labeled at the methyl position results in the dispersal of the label among various methyl-accepting compounds that appear in the plasma and may then enter the brain. One approach to overcoming this problem has been the use of "standard" corrections for the activity contributed to plasma by labeled plasma protein and labeled serine. In order to determine the validity of this approach, the metabolic fate of labeled methionine was studied in six dogs. After injection with either [C3H3] methionine or [14CH3] methionine arterial blood was sampled. Plasma fractions containing protein were separated by fast gel filtration, counted with standard scintillation techniques, and their radioactivity was compared with total plasma radioactivity. Plasma was also separated by high-pressure liquid chromatography into methionine, serine, and nonmethionine or serine-containing fractions. These fractions were counted, and their radioactivity was compared with total plasma radioactivity. Labeled protein appeared in plasma about 20 minutes postinjection and then increased steadily. Labeled serine also appeared and reached a peak value of 9.4 +/- 2.1% of plasma activity at 40 minutes. Of greatest interest was the appearance in later plasma samples of increasing amounts of activity contained in nonserine low molecular weight metabolites of methionine. At 40 minutes, those metabolites made up 27 +/- 6.9% of total plasma activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Considerations in the purchase of a nuclear medicine computer system.

Selection of a nuclear medicine computer system is a process that should be approached with care and forethought. The general scheme should be to define your needs and constraints, determine what is available, investigate the leading candidates, make a site visit, and, finally, submit an order. Through a series of discussions between members of the Computer Council of the Society of Nuclear Medicine and representatives from the manufacturers of computer systems, a set of important considerations emerged, which are reported in this paper. This paper is not intended to be a step-by-step guideline to the purchase of a computer system. Rather, it is a set of concepts and considerations with which the prospective purchaser should be familiar before undertaking such a purchase.

Computer Systems↗
PubMed1987

Localization of serotonin 5-HT2 receptors in living human brain by positron emission tomography using N1-([11C]-methyl)-2-Br-LSD.

N1-([11C]-Methyl)-2-Br-LSD ([11C]-MBL) has been developed as a positron emission tomography (PET) imaging agent for serotonin 5-HT2 receptors. In vitro receptor binding assays with nonradioactive MBL show high-affinity binding to serotonin 5-HT2 receptors (Ki = 0.5 nM), a secondary interaction of 8-fold lower affinity with dopamine D2 receptors, and low-affinity interactions with alpha 1-adrenergic as well as serotonin 5-HT1 receptors. Intravenous injection of [11C]-MBL in a baboon led to selective labeling of cortical regions that was markedly blocked by prior administration of ketanserin, a selective 5-HT2 receptor antagonist. Clinical trials with [11C]-MBL have been conducted in seven normal human volunteers, and the regional distribution of radioactivity in the brain was distinctly serotonergic. Labeling was highest in frontal, temporal, and parietal cortex with lower levels observed in caudate and putamen. The tracer rapidly washed from the cerebellum and the low levels of activity in this brain region were used to define nonspecific binding. The maximum specificity was reached between 30 and 60 minutes postinjection when frontal cortex to cerebellum ratios ranged from 1.7 for a 52-year-old male to 2.7 for a 30-year-old male. In agreement with previous studies, a trend towards lower ratios (lower serotonin 5-HT2 receptor levels) was observed in older volunteers. These studies indicate that [11C]-MBL is a selective radioligand that can be used to monitor serotonin 5-HT2 receptor densities in vivo in most regions of the human brain.

Animals↗
PubMed1987

On estimating the loss of quantification in PET due to finite detector resolution.

In positron emission computed tomography, images are reconstructed from projection data of the slice. Such projection data are inherently subject to bias owing to the detection of coincident annihilation photons with detectors of finite resolution. The influence of these unavoidable effects on reconstructed data is reviewed and a straight forward method is outlined for calculating the loss of quantification of small objects owing to finite detector resolution. A sample calculation using idealized point spread functions is presented.

Brain↗
PubMed1987

Artifacts in camera based single photon emission tomography due to time activity variation.

Image quality in single photon emission computed tomography (SPECT) using a rotating gamma camera is dependent on the time course of the tracer in the field of view. If acquisition times are slow compared to the tracer turnover, artifacts may occur in the reconstructed images. The properties of such artifacts were studied by computer simulation. Experimental projection data of point sources, cylindrical phantoms, and an anatomically realistic brain phantom were altered by sequentially weighting the projections with a function that varied exponentially or linearly with time. The observed distortion in the reconstructed images could be related to the ratio between the object activity variation and the camera rotation time. If the tracer concentration changed less than a factor of two during one camera rotation then little image distortion was visible although quantitatively the resolution was degraded. If the object's activity variation with time is fast enough to produce noticeable distortion, the artifacts can be reduced by performing multiple, rapid, camera rotations, instead of one rotation, for the same total acquisition time. The proposed procedure is computer storage space intensive and takes longer to produce the transaxial images, but improves image quality.

Image Enhancement↗
PubMed1987

Linear discriminant analysis of regional ejection fractions in the diagnosis of coronary artery disease.

We studied the application of linear discriminant analysis to the computer assisted interpretation of rest and exercise gated blood pool studies. Data were obtained in 45 patients in whom the presence or absence of coronary artery disease was determined by coronary angiography. Automated analysis of regional ejection fractions using a linear discriminant function (LDF) was compared to the fully automated calculation of global ejection fraction and to the subjective evaluation of wall motion. A LDF constructed from the data for the first 31 consecutive patients correctly classified 25/31 (81%). The change in global ejection fraction correctly classified 24/31 (77%) and wall motion analysis 25/31 (81%). In a distinct group of 14 patients the same LDF correctly classified 12/14 (86%), global ejection fraction 9/14 (64%) and wall motion analysis 10/14 (71%).

Coronary Disease↗
PubMed1987

Positron tomographic quantitation of neuroreceptors in human brain in vivo--with special reference to the D2 dopamine receptors in caudate nucleus.

The radioligand 3-N-[11C]methylspiperone (11C-NMSP) binds to D2 dopamine receptors with high affinity. We determined the rate of binding in 12 male volunteers, using a 3-compartment model to relate the time integral of the tracer plasma concentration to the distribution of the tracer in the caudate nucleus measured by positron tomography. The rate of binding (k3) was defined as the product of the bimolecular association rate (kon) and the quantity of available receptors (B'max). We calculated the product as the ratio between the steady-state rate of accumulation and the volume of distribution in the caudate nucleus. The average value was 0.100 min-1 in the normal volunteers. We varied k3 by reducing the number of available receptors with the D2 dopamine receptor blocking agent haloperidol ingested 4 hours before the tracer injection. In the normal volunteers, we calculated a receptor density of 17 pmol g-1 in the caudate nucleus and an inhibitory constant of haloperidol of 3 nM by comparing tracer accumulation in the absence and presence of the blocking agent. Bmax was also calculated in older men, drug-naive schizophrenics, and drug-treated schizophrenics (all men). The lowest value of Bmax was calculated in the older men (6 pmol g-1); the highest in the two groups of schizophrenic patients (39 and 41 pmol g-1, respectively).

Adult↗
PubMed1987

Radiosynthesis of a selective dopamine D-1 receptor antagonist: R(+)-7-chloro-8-hydroxy-3-[11C]methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3 -benzazepine ([11C]SCH 23390).

Carbon-11 labeled SCH 23390, a selective dopamine D-1 receptor antagonist (Fig. 1b), was prepared by N-alkylation of the nor-methyl precursor with [11C]iodomethane. The product was purified by semi-preparative HPLC and shown to be radiochemically pure at the end of synthesis. The synthesis was completed in approximately 22 min with an average radiochemical yield of 28% (based on [11C]iodomethane) and an average specific activity of approximately 1950 microCi/mumol calculated at the end of synthesis.

Benzazepines↗
PubMed1987

Lymphocyte abnormalities in infants born to drug-abusing mothers.

To evaluate the possible effects of maternal intravenous drug use on infant immunity, we measured the in vitro peripheral blood mononuclear cell proliferative responses to phytohemagglutinin (PHA) and pokeweed mitogen, T cell subset numbers, immunoglobulin levels, and titers of antibodies to cytomegalovirus (CMV) and human immunodeficiency virus (HIV) in a group of drug-abusing mothers and their infants. Infants of drug abusers had a lower proliferative response to mitogen, associated with altered kinetics of the maximum response to PHA. The OKT4/OKT8 ratio decreased with age in the drug-exposed infants compared with control infants (P less than 0.005). There was no evidence of CMV infection in either group. One mother and her infant had antibody to HIV. Our data demonstrate that infants of intravenous drug-using mothers have distinct immunologic differences at birth compared with non-drug-exposed infants and that these persist throughout the first year of life. The cause appears unrelated to intrauterine viral infection, suggesting a direct toxic effect of the drugs on fetal immunologic development.

Antibodies, Viral↗
PubMed1987

Comparison of 99Tcm complexes (NEP-DADT, ME-NEP-DADT and HMPAO) with 123IAMP for brain SPECT imaging in dogs.

Several new lipophilic 99Tcm complexes have recently been described as alternatives to N-isopropyl (123I) iodoamphetamine (123IAMP) for measurement of regional cerebral blood flow (RCBF). In this study we have compared brain uptake and blood clearance of 99Tcm-N-ethylpiperidine-diamino dithiol (99Tcm-NEP DADT), its 4-methylated derivative (99Tcm-Me-NEP-DADT) and 99Tcm-hexamethyl-propylene-amine-oxime (99Tcm-HMPAO) with that of 123IAMP in two dogs. Single photon emission tomography (SPECT) was employed to measure brain accumulation and retention of the four radiopharmaceuticals. Cerebral uptake of the 99Tcm complexes (0.8-1.1%) was lower than that of 123IAMP (1.6% of the injected dose). There was considerable extracerebral activity in the dog's head, especially in the olfactory and snout regions. Because of slow blood clearance 99Tcm-HMPAO showed high uptake in these regions. Brain uptake of 99Tcm-HMPAO reached a plateau 5 to 10 min after intravenous injection and remained constant for the entire study period (1 h). 99Tcm-NEP-DADT, on the other hand, showed significant clearance from the brain after reaching maximal uptake at 10 to 15 min after injection. However, brain imaging with these agents was possible during the first 20 min. The mechanism of brain uptake, as well as the relationship between brain uptake and RCBF need to be evaluated for each of the four radiopharmaceuticals.

Amphetamines↗
PubMed1987

Unexpected thymic hyperplasia in transgenic mice harboring a neuronal promoter fused with simian virus 40 large T antigen.

The hypothalamic peptide growth hormone-releasing factor (GRF) regulates the secretion and production of growth hormone from the anterior pituitary (M. C. Gelato and G. R. Merriam, Annu. Rev. Physiol. 48:569-591). To study GRF gene regulation, transgenic mice were generated that harbor the human GRF promoter fused to the coding sequences from the simian virus 40 early region. These mice had normal hypothalamic functions but unexpectedly suffered from severe thymic hyperplasia. Immunohistochemical analysis revealed that large T antigen was expressed in the thymic epithelial cells. These cells have endocrine properties and are known to produce thymic hormones [corrected]. The thymic hyperplasia was the apparent consequence of inappropriate production of T-cell maturation factors by epithelial cells and could involve increased self renewal of apparently normal T stem cells in the thymus.

Animals↗
PubMed1986

Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics.

In postmortem studies of patients with schizophrenia, D2 dopamine receptors in the basal ganglia have been observed to be more numerous than in patients with no history of neurological or psychiatric disease. Because most patients with schizophrenia are treated with neuroleptic drugs that block D2 dopamine receptors in the caudate nucleus, it has been suggested that this increase in the number of receptors is a result of adaptation to these drugs rather than a biochemical abnormality intrinsic to schizophrenia. With positron emission tomography (PET), the D2 dopamine receptor density in the caudate nucleus of living human beings was measured in normal volunteers and in two groups of patients with schizophrenia--one group that had never been treated with neuroleptics and another group that had been treated with these drugs. D2 dopamine receptor densities in the caudate nucleus were higher in both groups of patients than in the normal volunteers. Thus, schizophrenia itself is associated with an increase in brain D2 dopamine receptor density.

Adult↗
PubMed1986

Positron emission tomographic study of D2 dopamine receptor binding and CSF biogenic amine metabolites in Rett syndrome.

We report on the first positron emission tomographic study of dopamine receptor binding in Rett syndrome. The patient is a 25 year old Austrian woman diagnosed at age 2 and followed since then by Rett. A computed axial tomogram (CT scan) showed cortical atrophy, and enlarged ventricles but normal structure of the caudate/putamen. Following the CT scan 20 mCi of 11 C N-methyl spiperone, a butyrophenone with a high affinity for dopamine D2 receptors was administered intravenously. The patient was found to have dopamine D2 receptor binding activity in the low normal range. The caudate/cerebellar activity ratio was below the mean regression line (p = 0.10) that relates the CA/CB ratio as a function of age. Levels of cerebrospinal fluid neurotransmitter metabolites were normal.

Adult↗
PubMed1986

Quantification of neuroreceptors in the living human brain. I. Irreversible binding of ligands.

A first step in the quantification of receptor density in the living human brain is the measurement of the binding of a labeled ligand to the receptor in question. In the present study, we determined the rate of binding of 11C-labeled N-methylspiperone (NMSP) to the D2 dopamine receptor in 11 normal volunteers, using a three-compartment model to relate the time integral of the measured plasma concentration to the distribution of the tracer in the caudate nucleus. The plasma concentrations of NMSP were separated from the contaminating metabolites by the ratio of radioactivities in cerebellum and blood plasma. Plasma concentrations calculated in this way agreed with plasma concentrations determined by HPLC. The rate of binding of labeled NMSP to its receptors (k3) was defined as the product of the bimolecular association rate (kon) and the quantity of available receptors (B'max) and calculated as the ratio between the steady-state rate of accumulation and the volume of distribution of labeled NMSP in the caudate nucleus. The average value of k3 in the 11 normal volunteers was 0.065 min-1. The fractional clearance of labeled NMSP from the caudate nucleus (k2) was 0.070 min-1 and thus close to the value of k3. We also examined several indexes of binding based on ratios between different regions in brain. The indexes required that binding be negligible compared to the efflux of labeled NMSP (i.e., k2 much greater than k3) and therefore yielded incorrectly low values of k3. Thus, the only accurate approach used measured plasma concentrations to estimate transfer constants at steady state and yielded the absolute rate of binding k3. The approach is applicable to other irreversibly bound ligands.

Adolescent↗
PubMed1986

Quantification of Neuroreceptors in the living human brain. II. Inhibition studies of receptor density and affinity.

A method for estimating receptor density (Bmax) in the living human brain by positron emission tomography was exemplified by a ligand, 3-N-[11C]methylspiperone ([11C]NMSP), that binds to D2 dopamine receptors with high affinity. The ligand binds essentially irreversibly (i.e., with very little dissociation) to the receptors during the 2-h scanning period. Transfer constants were estimated at steady state. In a previous article, we presented a method for the determination of k3, the rate of binding of the labeled ligand. In the present work, we varied k3 by reducing the number of available receptors with a previously administered receptor blocking agent, haloperidol. We calculated a receptor density of 9.2 pmol g-1 in the caudate nucleus of four normal volunteers, and an inhibitory constant of haloperidol of 1.4 nM by comparing tracer accumulation in the absence and the presence of the blocking agent. The values agreed with measurements of NMSP receptor density and haloperidol inhibitory potency in vitro in brain homogenates from human autopsy material.

Adolescent↗
PubMed1986

3H-3-N-methylspiperone labels D2 dopamine receptors in basal ganglia and S2 serotonin receptors in cerebral cortex.

Detailed studies of the properties of 3H-3-N-methylspiperone (NMSP) binding in rat and human brain homogenates were performed at 37 degrees C. In homogenates of rat striatum and frontal cortex and human caudate and frontal cortex tissues, the specific binding was found to be saturable. Rat caudate contained 33.2 pmol/gm wet-weight tissue and displayed an equilibrium dissociation constant (Kd) of 8.7 X 10(-11) M; rat frontal cortex contained 18.5 pmol/gm wet-weight tissue and displayed a Kd of 1.5 X 10(-10) M. Human caudate contained 8.96 pmol/gm wet-weight tissue and displayed a Kd of 1.1 X 10(-10) M; human frontal cortex possessed 9.8 pmol/gm wet-weight tissue and a Kd of 4.4 X 10(-10) M. Kinetic studies revealed a very rapid rate of association in all the tissues studied. The rate of dissociation was relatively slow in all 4 tissue preparations; the dissociation rate was somewhat slower in rat striatum and human caudate relative to rat and human frontal cortex. This was consistent with the somewhat higher affinity, relative to frontal cortex, displayed by 3H-NMSP in rat striatal and human caudate tissue. The pharmacological properties of the specific binding in rat striatal and human caudate tissues were very similar and indicated the presence of brain D2 dopamine receptors. In rat and human frontal cortex tissue homogenates, the pharmacological characteristics of the specific binding indicated the presence of 5-HT2 receptors.

Animals↗
PubMed1986

Simplified detection system for neuroreceptor studies in the human brain.

A simple, inexpensive dual-detector system has been developed for measurement of positronemitting receptor-binding drugs in the human brain. This high efficiency coincidence counting system requires that only a few hundred microcuries of labeled drug be administered to the subject, thereby allowing for multiple studies without an excessive radiation dose. Measurement of the binding of [11C]carfentanil, a high affinity synthetic opiate, to opiate receptors in the presence and in the absence of a competitive opiate antagonist indicates the potential utility of this system for estimating different degrees of receptor occupation in the human brain.

Binding, Competitive↗