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Biomedical subjects

D R Christman

Publications and source records attributed to D R Christman.

At least 19 recordsLinked to original sources
PubMed1992

Is [1-11C]putrescine useful as a brain tumor marker?

Our experience with 11C-putrescine underscores the difficulty of finding a selective brain tumor tracer, uniquely incorporated by neoplastic glia or metastatic cells within brain, but not by the proliferating, nontransformed cells which constitute a normal pathophysiological reaction to various disease processes. Thirty-three patients with 36 lesions were studied with 11C-putrescine to determine the specificity of labeled putrescine for tumor tissue. The uptake of 11C-putrescine was correlated with local cerebral glucose metabolic rate in various lesions, including different types of tumors, to assess the relationship between 11C-putrescine uptake and tumor biology. Carbon-11-putrescine uptake was similar in malignant tumor and benign, non-neoplastic lesions with blood-brain barrier breakdown, illustrating the lack of tumor specificity of this tracer. Carbon-11-putrescine was not well incorporated into poorly enhancing lesions, regardless of their pathology, emphasizing the requirement of a disrupted blood-brain barrier for 11C-putrescine uptake. The ratio of 11C concentration within lesions, compared to that in a region of interest in the contralateral brain, weakly correlated with an analogous ratio for local cerebral glucose metabolic rate in various lesions. Physiological processes not unique to tumors are associated with polyamine active transport and metabolism and contribute to the lack of tumor specificity of 11C-putrescine. Carbon-11-putrescine appear to have less diagnostic utility than 18FDG in brain tumors. The potential of 11C-putrescine for evaluating the effect of antineoplastic therapy and providing prognostic information on brain tumors remains to be investigated.

Biomarkers, Tumor↗
PubMed1989

Altered glucose metabolism in microvessels from patients with Alzheimer's disease.

Microvessels isolated from temporal cortex of patients with Alzheimer's disease showed decreased uptake of glucose when compared with vessels from age-matched or young control subjects. This was due to decreased hexokinase activity in the Alzheimer samples, as determined by ion exchange chromatography. This finding was confirmed independently by determination of the phosphorylation constant for hexokinase, K3, using positron emission tomography. The results suggest that Alzheimer's disease may result from a global defect in brain energy metabolism.

Adult↗
PubMed1988

Reproducibility of cerebral glucose metabolic measurements in resting human subjects.

Positron emission tomography with 11C-2-deoxyglucose was used to determine the test-retest variability of regional cerebral glucose metabolism in 22 young normal right-handed men scanned twice in a 24-h period under baseline (resting) conditions. To assess the effects of scan order and time of day on variability, 12 subjects were scanned in the morning and afternoon of the same day (a.m.-p.m.) and 10 in the reverse order (p.m.-a.m.) with a night in between. The effect of anxiety on metabolism was also assessed. Seventy-three percent of the total subject group showed changes in whole brain metabolism from the first to the second measurement of 10% or less, with comparable changes in various cortical and subcortical regions. When a scaling factor was used to equate the whole brain metabolism in the two scans for each individual, the resulting average regional changes for each group were no more than 1%. This suggests that the proportion of the whole brain metabolism utilized regionally is stable in a group of subjects over time. Both groups of subjects had lower morning than afternoon metabolism, but the differences were slight in the p.m.-a.m. group. One measure of anxiety (pulse at run 1) was correlated with run 1 metabolism and with the percentage of change from run 1 to run 2. No significant run 2 correlations were observed. This is the first study to measure test-retest variability in cerebral glucose metabolism in a large sample of young normal subjects. It demonstrates that the deoxyglucose method yields low intrasubject variability and high stability over a 24-h period.

Adolescent↗
PubMed1987

Alteration of regional cerebral glucose metabolic rate in non-Korsakoff chronic alcoholism.

That chronic alcoholism yields devastating effects to the central nervous systems of its victims is well known, but the actual physiologic mechanisms underlying that deterioration have yet to be completely identified. What is also known is that many chronic alcoholics seem to recover brain function after a protracted period of abstinence, but the actual mechanisms of that restoration are also not well understood. Using positron emission tomography with the tracer 11C-2-deoxy-D-glucose as a probe to measure regional cerebral metabolic rate of glucose (RCMRGlu), we compared the magnitudes of glucose consumption in 44 brain regions between a group of newly abstinent chronic alcoholics without Korsakoff's psychosis and a control group of normal nonalcoholic subjects whose range of age was that of the alcoholic group. We found that RCMRGlu measurements in the brains of alcoholics were significantly lower than in the brains of the control group, and that there were many fewer significant interregional correlations in the brains of the alcoholics than in the brains of the control group. We also found no significant correlation between age and global metabolic rate of glucose in either group. However, even though the number of alcoholic subjects was too few to allow a reliable statistical comparison, the measurements suggest that chronic alcoholics over the age of 50 years suffer a greater decrease of RCMRGlu values than do their counterparts under the age of 50 years. While resting in a bland environment, neither alcoholic nor control subjects were found to have significant differences in RCMRGlu values between their brain hemispheres. In contrast to this similarity, normal dextrous subjects responded to a nonverbal auditory stimulus by increasing the metabolic rate of glucose in their right hemispheres while eight of nine chronic alcoholics did not. The results of this pilot study point to arguments that the alcoholic brain metabolizes glucose at a lower rate than do normal brains, that there are fewer region-to-region functional relationships in the alcoholic brain than in the normal brain, and that alcoholics may be impaired in right hemispheric processing. In subsequent investigations, we will measure the metabolic changes that follow abstinence, if any, by tracking subjects throughout an interval of rehabilitation. Also, we intend to test the findings of this study by measuring greater numbers of alcoholic subjects to separate the consequences of measurement variability, age, and chance from the underlying biologic processes that seem to be affected by chronic alcoholism.

Adult↗
PubMed1987

Serial PET studies of human cerebral malignancy with [1-11C]putrescine and [1-11C]2-deoxy-D-glucose.

Serial PET measurements of [1-11C]putrescine ([11C]PUT) uptake and glucose metabolic rate (GMR) using [1-11C]2-deoxy-D-glucose ([11C]2DG) were made on eight human subjects with a radiological and, in most cases, pathological diagnosis of primary or metastatic brain tumor. Blood-to-brain influx constants (Ki) were calculated for [11C]PUT. Tumor uptake of 11C after [11C]PUT injection was unidirectional peaking at 15 min. The mean +/- s.d. Kis for [11C]PUT for tumor and normal brain tissue were 0.78 +/- 0.045 and 0.024 +/- 0.007 ml cc-1 min-1, respectively (average of ratio, 3.11) whereas the ratio of GMR for tumor and normal brain tissue was 1.2 +/- 0.5. The mean Ki for four active, high grade astrocytomas was 0.098 +/- 0.030 in contrast to 0.027 +/- 0.008 ml cc-1 min-1 for two patients with low grade astrocytoma. Active high grade astrocytomas also showed marked CT contrast enhancement and regional glucose hypermetabolism. In one subject with brain metastases, both [11C]PUT and GMR correlated with a declining clinical picture in repeated studies over a 4-mo period. PET studies with [11C]PUT provide a better signal:noise ratio than GMR measurements, are useful for locating small glycolytically hypometabolic tumors and, when used in longitudinal studies in a single subject, appear to provide an index of degree of malignancy.

Adult↗
PubMed1986

Effect of reserpine on regional cerebral glucose metabolism in control and migraine subjects.

The regional cerebral metabolic rate of glucose metabolism (RCMRGlu) in five headache and six control subjects was measured with positron emission tomography (PET) using the tracer 2-deoxy-D-[1-11C] glucose before and after the administration of reserpine. The short half-life of the carbon 11 tracer made possible a test-retest paradigm wherein each subject served as his own control in assessing the effect of reserpine on RCMRGlu. Thus, measurements were first performed with subjects at rest and subsequently at 1 1/2 hours after the parenteral administration of reserpine (rest-reserpine). In control subjects without history of migraine, reserpine did not induce headache, and, furthermore, PET measurements 1 1/2 hours after drug administration consistently showed a global increase in RCMRGlu over resting values similar to that observed in a normal control (rest-rest) group not receiving reserpine. By contrast, four of the five subjects with migraine began to experience a mild unilateral headache or visual disturbances 1 1/2 hours after reserpine, at which time PET scanning showed a 5% to 30% decline in RCMRGlu below the values that had been measured before reserpine injection, all well outside of the 99% confidence limits of normal variation separately determined on 25 control subjects (rest-rest). There was no apparent laterality, and subjects with a history of either common or classic migraine responded in a similar manner. The difference in percent change in RCMRGlu following administration of reserpine observed in these four subjects with migraine headaches was significantly different over all regions of interest as compared with all six control subjects receiving the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Improved delineation of human dopamine receptors using [18F]-N-methylspiroperidol and PET.

The brain uptake of [18F]-N-methylspiroperidol, a butyrophenone neuroleptic with high selectivity for the dopamine receptor, has been measured in three normal human volunteers using positron emission tomography for times up to 12 hr postinjection. These studies demonstrated two unique findings concerning the in vivo distribution of this neuroleptic: (a) it is tightly bound to dopamine D-2 receptors in the caudate-putamen brain regions, and (b) these regions are the only large brain structures which exhibit appreciable long-term retention. In addition, radioactivity clears rapidly from plasma, and the percentage of unchanged [18F]-N-methylspiroperidol in plasma declines rapidly. These results suggest that this compound binds irreversibly to dopamine D-2 receptors, and that there are few if any dopamine D-2 receptors in the human frontal cortex. These studies emphasize not only the importance of characterizing neurotransmitter receptors in living human brain using a ligand labeled with a positron emitting nuclide of sufficiently long half-life to allow monitoring of brain radioactivity distribution for several hours after the injection of radioligand, but also of accurately determining the amount of unchanged tracer in plasma for tracer kinetic modeling.

Adult↗
PubMed1984

Human primary visual cortex topography imaged via positron tomography.

The visuotopic structure of primary visual cortex was studied in a group of 7 human volunteers using positron emission transaxial tomography (PETT) and 18F-labeled 2-deoxy-2-fluoro-D-glucose ( [18F]DG). A computer animation was constructed with a spatial structure which was matched to estimates of human cortical magnification factor and to striate cortex stimulus preferences. A lateralized cortical 'checker-board' pattern of [18F]DG was stimulated in primary visual cortex by having subjects view this computer animation following i.v. injection of [18F]DG. The spatial structure of the stimulus was designed to produce an easily recognizable 'signature' in a series of 9 serial PETT scans obtained from each of a group of 7 volunteers. The predicted lateralized topographic 'signature' was observed in 6 of 7 subjects. Applications of this method for further PETT studies of human visual cortex are discussed.

Deoxyglucose↗
PubMed1984

Regional brain glucose metabolism in chronic schizophrenia. A positron emission transaxial tomographic study.

Thirteen diagnosed schizophrenics and 11 normal controls were studied with a method using the PETT III positron emission tomograph (PET) and fluorodeoxyglucose labeled with fluorine 18. Each subject also had a computed tomographic (CT) scan. For each subject, two brain levels, one through the basal ganglia and one through the semioval center, were analyzed for the mean regional metabolic glucose rate. Specifically, relationships between frontal and posterior regions were evaluated. The CT scans of matching levels were superimposed on the functional PET images to provide anatomic criteria for region of interest selection. While no whole-slice metabolic differences were apparent between groups, schizophrenics had significantly lower activity in the frontal lobes, relative to posterior regions. The medicated and drug-free groups did not differ from one another in these regards. Trait v state dependency of the phenomenon was analyzed, and several technological limitations were considered.

Adult↗
PubMed1984

Patterns of metabolic activity in the treatment of schizophrenia.

Six patients with chronic schizophrenia were studied with positron emission tomography (PET) before and after neuroleptic treatment, using fluorine-18-labeled fluorodeoxyglucose. After treatment, the mean whole-slice glucose metabolic rate at the level of the basal ganglia showed a 25% increase. However, patterns of frontal hypometabolism observed with the schizophrenic patients were not altered by medication. Pattern analysis using the fast Fourier transform was applied to a set of 422 images from a mixed group of normal, depressed, and schizophrenic subjects. Reconstruction of the images with low-frequency coefficients was excellent, reducing considerably the number of variables needed to characterize each image. Hierarchical cluster analysis categorized the transformed images according to anatomical level and subject group (patient versus control). The results suggest the utility of this procedure for the classification and characterization of metabolic PET images from psychiatric patients.

Adult↗
PubMed1984

Positron emission tomography and computed tomography assessments of the aging human brain.

The relationship between alterations in brain structure and brain function was studied in vivo in both young and elderly human subjects. Computed tomography revealed significant age-related ventricular and cortical sulcal dilatation. The cortical changes were most closely related to age. Positron emission tomography failed to show regional changes in brain glucose metabolic rate. The results suggest that the normal aging brain undergoes structural atrophic changes without incurring regional metabolic changes. Examination of the correlations between the structural and the metabolic measures revealed no significant relationships. These data are discussed with respect to the significant structure-function relationships that have been reported in Alzheimer disease.

Adult↗
PubMed1983

Cyclotron isotopes and radiopharmaceuticals--XXXIII. Synthesis and structural effect of selective biliary excretion of halogenated indotricarbocyanines.

Five indotricarbocyanines of structure I were synthesized and labeled with 131I in the 5 position. The substituent, R, was varied [formula: see text] R = H, F, Cl, Br and I. The dynamics of hepatic uptake and blood clearance of the labeled compounds were determined in mice. Kidney uptake in all cases was negligible. The hepatic excretion displayed 2 components. The initial hepatic disappearance rates of R = H and R = F were 7.3 and 4.5%/min, respectively. The maximum liver activity in mice occurred at 2--5 min and the % remaining in the liver at 0.5 h was 3.6, 8.6, 19, 29 and 47% for R = H, F, Cl, Br and I substitution. It is notable that a small change in the substituent at the 5' position in the molecule has such a pronounced effect. Whether electronic and/or steric effects are controlling the mechanism of hepatobiliary clearance is not obvious. A correlation of the liver activity with the covalent radius of R was noted. The comparative studies were at an injected dose of 0.4--0.6 mumol/kg, and typically at a specific activity of 200 mCi/mol. Loading dose effects were not appreciable under these conditions. Scintigraphic results are reported for dogs and a rabbit. The results suggest that indotricarbocyanines of structure (I) labeled with 123I or with 18F are potential radiopharmaceuticals for dynamic hepatobiliary function studies.

Animals↗
PubMed1983

Computed tomography and positron emission transaxial tomography evaluations of normal aging and Alzheimer's disease.

Young normal subjects, old normal subjects, and patients with senile dementia of the Alzheimer's type (SDAT) were studied with both computed tomography (CT) and positron emission transaxial tomography (PETT). Increases in ventricular size with both aging and disease were measured. Regional glucose metabolic rate was not affected by age, but was markedly reduced in SDAT patients. These data indicate that in normal aging, structural brain changes may be more salient than biochemical changes. Although both structural and biochemical changes occur in SDAT, the biochemical changes are more marked. The results suggest that PETT is potentially more useful than CT in the in vivo diagnosis of SDAT.

Adult↗
PubMed1982

Increased accumulation of 2-deoxy-2-[18F]Fluoro-D-glucose in liver metastases from colon carcinoma.

Three patients with liver metastases from colon carcinoma were studied with 2-deoxy-2-[F-18]fluoro-d-glucose (F-18-FDG) using positron emission tomography. The radioactivity in the metastatic tumor increased continuously following the injection of F-18-FDG, whereas it decreased in normal liver tissue. This resulted in the tumor to normal-liver ratio of 3.3-4.7 at 50 min after injection. The liver tumor was visualized as an increased accumulation of radioactivity in all patients, with the central area of the tumor showing less activity. These preliminary results suggest that F-18-FDG may be useful as a positive imaging agent for the detection and characterization of liver tumors.

Adenocarcinoma↗
PubMed1980

Radioactive phosphorus uptake test. An in vitro analysis of choroidal melanoma and ocular tissues.

The concentration of radioactive phosphorus in uveal melanoma and normal parts of the eye was determined in vitro in 14 eyes. The eyes were enucleated after a positive 32P uptake test. Portions of the melanoma as well as normal choroid, retina, sclera, lens, and vitreous were analyzed. The 32P uptake test had been performed at various intervals after intravenous administration of 32P from 24 to 556 hr. The in vitro uptake of 32P was compared to cell type, tumor volume, time of testing, percent uptake measured clinically, and specific activity. The only positive correlation was between percent uptake measured clinically and 32P concentration (dpm/gm). A higher concentration of phosphorus in melanoma resulted when carrier-free 32P was used. A negative correlation existed between number of hours from injection to clinical measurement of percent uptake, although melanoma to normal choroid ratios did not change from 24 to 72 hr. No correlation was found between uptake and tumor volume. The sample was small; however, we saw no correlation between 32P uptake and degree of malignancy.

Aged↗