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Biomedical subjects

T Ido

Publications and source records attributed to T Ido.

At least 181 records · Page 10Linked to original sources

Regional coupling of blood flow and methionine uptake in an experimental tumor assessed with autoradiography.

Regional distribution of L-[methyl-14C] methionine (14C-MET) and 4-[18F] fluoro-antipyrine was compared using experimental rat tumors (AH109A) and a computerized autoradiogram image processor. Tissue distributions of the two tracers were found to be inhomogeneous in the tumor with nearly identical image patterns. Analysis of tissue radioactivities revealed that 82% of 14C-MET was derived from the acid insoluble fraction at 60 min after injection. The present study showed that 14C-MET uptake closely relates to tissue blood flow and may depend on its blood to tissue transport. Rapid incorporation of MET in the acid insoluble fraction implies that it is rapidly metabolized after transport into tumor tissue.

Animals↗

Positron CT imaging of an impending stroke.

We present PET findings of a case of a transient ischemic attack which later progressed to cerebral infarction. Cerebral blood flow at the stroke focus in the right parietal cortex measured after a TIA attack and before stroke was as low as 24 ml/100 g/min with some increase in oxygen extraction fraction and blood volume. The condition was compatible with "misery perfusion". This case may be an example suggestive that the "misery perfusion sign" is a warning of impending stroke and its poor prognosis if left without appropriate treatments.

Aged↗

Increased amounts of D-enantiomer dependent on alkaline concentration in the synthesis of L-[methyl-11C]methionine.

The presence of D-enantiomer in L-[methyl-11C]methionine prepared from [11C]CH3I and L-homocysteine thiolactone, was measured by high performance liquid chromatography using a reverse-phase column with an eluent containing L-proline and cupric acetate. The amount of D-enantiomer increased with concentration of NaOH used. The reaction time, 2-10 min, and the reaction temperature, 40 degrees-80 degrees C, have only minor effect on the formation of D-enantiomer. No significant difference was found for three different lots of L-homocysteine thiolactone. At the highest concentration investigated, 1.0 M NaOH in 50% aqueous acetone, the percentage of D-enantiomer was found to be 7.7%. With 0.025 M NaOH used only 2.1% was measured. When L-[methyl-11C]methionine was incubated in 1.0 M NaOH, no conversion of L- into D-enantiomer was observed.

Carbon Radioisotopes↗

Automated synthesis system with computer control for the production of [1-11C]fatty acids.

To accommodate the increasing need for [1-11C]fatty acids for use in routine medical studies and the large amounts of radioactivity required, a more advanced automated synthesis system for the preparation of [1-11C]fatty acids has been constructed. The synthesis of [1-11C]fatty acids has been completely automated using a new separation unit (isobaric Sepaltor) for the extraction procedure, which had caused some difficulties with automation. The yield of [1-11C]palmitic acid was 20-30 mCi, and that of 3-methyl [1-11C]heptadecanoic acid was 2-7 mCi. The time required for the synthesis was less than 30 min from the start of the 11CO2 trapping. This system has been used for more than 20 preparations of [1-11C]palmitic acid and more than 20 preparations of 3-methyl [1-11C]heptadecanoic acid.

Carbon Radioisotopes↗

Synthesis and biodistribution of [11C]fludiazepam for imaging benzodiazepine receptors.

As a tracer for in vivo studies on benzodiazepine receptors, 7-chloro-1,3-dihydro-5-(2-fluorophenyl)-1-[11C]methyl-2H-1,4- benzodiazepin-2-one, [11C]fludiazepam, was synthesized by the methylation of nor-derivative with [11C]CH3I, and purified by high-performance liquid chromatography. Within 60 min [11C]fludiazepam was obtained for injection in high radiochemical yields and in high radiochemical purity with a specific activity of up to 230 mCi/mumol. After i.v. injection of [11C]fludiazepam in rats the radioactivity was rapidly incorporated into many tissues and the blood clearance of the radioactivity was very rapid. The brain uptake was high and decreased gradually. The adrenal uptake was the highest and decreased with high loading doses. The effect of the loading dose on the uptake was also found in the heart and lungs. By autoradiography using [11C]fludiazepam, a higher accumulation was visualized in the cortex and thalamus than in other regions.

Animals↗

Enhanced glucose metabolism and impaired placental function in hypoxic pregnant rats.

Glucose metabolism using 2-deoxy-2-[18F]fluoro-D-glucose [( 18F]FDG) was studied in experimental hypoxia (10% oxygen concentration) of pregnant rats with special attention given to the placental function. After an i.v. injection of [18F]FDG, the uptake of 18F increased with time in the maternal brain, placenta and fetus of control rats. In the hypoxic condition, the uptake in these tissues was enhanced significantly, especially in the maternal brain and fetal heart, brain and lungs. A double-label autoradiography with [18]FDG and [14C]iodoantipyrine [( 14C]IAP) was performed to elucidate changes of the placental function in the hypoxic condition. The [18F]FDG image revealed a higher accumulation in the maternal side of the placenta of a control pregnant rat than in its fetal side. [18F]FDG uptake increased in the fetal brain and heart of hypoxic rats. The [14C]IAP image demonstrated that in the control rat there was a clear border zone on the maternal side of the placenta with very low permeability into the fetus. On the other hand, a high and heterogenous accumulation in both placenta and fetal organs was shown in hypoxic rats. We interpret this data to suggest that in a hypoxic condition the function of the placenta as a barrier system is impaired.

Animals↗

Tumor uptake studies of D,L-[5-14C]ornithine and D,L-2-difluoromethyl [5-14C]ornithine.

The feasibility of D,L-[5-14C]ornithine ([14C]ornithine), a precursor for polyamine synthesis, and D,L-2-difluoromethyl[5-14C]ornithine ([14C]DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC) were investigated for tumor localization. As an animal model, mice bearing mammary carcinoma, FM3A, were used. After i.v. injection of [14C]ornithine accumulation of radioactivity was observed in the FM3A, in which 43% of the 14C radioactivity was measured in the polyamine pool and 41% in the amino acid pool at 60 min after injection. Tumor uptake of [14C]DFMO was relatively low but constant during 60 min after injection. At 60 min after injection, 11% of the 14C was present in the acid-precipitable fraction of the FM3A, which suggests the formation of an irreversible complex of [14C]DFMO with ODC. For both compounds rapid blood clearance and high tumor-to-organ ratios were observed. Our results indicate that in connection with an enhanced polyamine synthesis in the tumors, the compounds investigated have potential as tracers for tumor detection.

Animals↗

Tumor uptake studies of S-adenosyl-L-[methyl-11C]methionine and L-[methyl-11C]methionine.

Tumor accumulation of S-adenosyl-L-[methyl-11C]methionine ([11C]SAM) was investigated in mice bearing mammary carcinoma (FM3A) and in rats bearing ascitic hepatoma (AH109A). After injection of [11C]SAM the blood clearance of 11C radioactivity was rapid. The 11C level was relatively high in both tumors. The uptake ratios of tumor to organ increased with time in several organs, especially in brain and muscle. In FM3A tumor tissue the 11C was incorporated with time into the acid-precipitable fraction and 38% of the 11C was detected in this fraction at 60 min after injection. This fraction reflects the amount of 11C-methyl group transferred into macromolecules in tumor tissue. In AH109A-bearing rats the metabolisms of [11C]SAM and L-[methyl-11C]methionine ([11C]Met), in vivo precursor of SAM, were compared. Tumor uptake of [11C]SAM was about two thirds of that of [11C]Met at 20 min after injection. At this time, for the [11C]SAM 27 and 8% of the 11C in the AH109A tissue were detected in the acid-precipitable and the lipid fractions, respectively. The corresponding figures for [11C]Met were 61% and 2%. In the liver considerable amounts of 11C were observed in the lipid fraction for both tracers. These results show that [11C]SAM has potential as a tracer for tumor localization with positron emission tomography (PET) and suggest that in tumor studies combining [11C]Met and PET, it should be taken into account that the 11C-labeled methyl group of [11C]Met is not only incorporated into protein but also other macromolecules and lipids via [11C]SAM.

Animals↗

Accumulation of 2-deoxy-2-[18F]fluoro-D-galactose in the liver by phosphate and uridylate trapping.

To investigate the highest accumulation of 2-deoxy-2-[18F]fluoro-D-galactose ([18F]FdGal) in the liver, metabolic studies with [18F]FdGal were carried out in Wistar rats for 120 min after i.v. injection. As main metabolites 2-deoxy-2-[18F]fluoro-D-galactose 1-phosphate ([18F]FdGal-1-P) and UDP-2-deoxy-2-[18F]-fluoro-D-galactose (UDP-[18F]FdGal) were identified in the liver and other tissues. The [18F]FdGal was phosphorylated by galactokinase. The phosphorylation rate was very rapid in the liver, in which at 5 min after injection 81% of 18F was detected as [18F]FdGal-1-P. After this time the phosphate form decreased with time, which was explained by conversion of [18F]FdGal-1-P to UDP-[18F]FdGal by UDP-glucose: galactose-1-phosphate uridyltransferase. At 120 min after injection 77% of the 18F was measured in the UDP-[18F]FdGal. In the brain both reaction rates were slower than in the liver. Both phosphate and uridylate derivates were also observed as main metabolites in the heart, lung, spleen and small intestine. On the other hand, a small amount of [18F]FdGal-1-P was detected in the plasma, in which the percentage of phosphate increased gradually and was 6% at 120 min. These results show that the [18F]FdGal metabolism in tissue results in phosphate and uridylate trapping and that the [18F]FdGal has potential for measuring in vivo galactose metabolism with positron emission tomography.

Animals↗

Measurement of the ratio of cerebral oxygen consumption to glucose utilization by positron emission tomography: its consistency with the values determined by the Kety-Schmidt method in normal volunteers.

The regional interrelationship between cerebral oxygen consumption (CMRO2) and cerebral glucose utilization (CMRGlc) was studied in normal subjects using positron emission tomography (PET) and the 15O steady-state inhalation and the [18F]fluoro deoxyglucose method. The use of standard sets of rate constants and the model lumped constant of 0.52 as well as the regional blood-brain partition coefficient for water and the blood volume correction for oxygen extraction fraction provided a CMRO2/CMRGlc ratio of 4.89 in the cortical gray matter, 5.27 in the basal ganglia and 5.82 in the centrum semiovale (white matter). The values of CMRO2/CMRGlc for the basal ganglia and the white matter were consistent with those reported for the whole brain with the Kety-Schmidt method. There was no significant difference in the CMRO2/CMRGlc between the basal ganglia and the white matter indicating the similar nature of in vivo oxidative metabolism of glucose in neuron-rich region and glial cell-rich region.

Aged↗

Cerebral glucose utilization in pediatric neurological disorders determined by positron emission tomography.

We measured local cerebral glucose utilization in 19 patients with Lennox-Gastaut syndrome (LG), partial seizures (PS), atypical and classical phenylketonuria (PKU), Leigh disease, and subacute sclerosing panencephalitis (SSPE), using positron emission tomography (PET). The mean values of regional glucose utilization in interictal scans of LG were significantly reduced in all brain regions when compared with that of PS (P less than 0.005). PET studies of glucose utilization in LG revealed more widespread hypometabolism than in PS. Two siblings with dihydropteridine reductase deficiency, a patient with classical PKU, and a boy with cytochrome c oxidase deficiency showed reduced glucose utilization in the caudate and putamen. A marked decrease in glucose utilization was found in the cortical gray matter of a patient with rapidly progressive SSPE, despite relatively preserved utilization in the caudate and putamen. The PET study of a patient with slowly progressive SSPE revealed patterns and values of glucose utilization similar to those of the control. Thus, PET provided a useful clue toward understanding brain dysfunction in LG, PS, PKU, Leigh disease, and SSPE.

Adolescent↗

Optimization of [11C]HCN production and no-carrier-added [1-11C]amino acid synthesis.

The optimal conditions for the catalytic production of [11C]HCN from [11C]CO2 were investigated. [11C]CO2 was reduced to [11C]CH4 with H2 on Ni and then converted to [11C]HCN by reaction with NH3 on Pt in a radiochemical yield of more than 95% under the optimized conditions of an NH3 concentration of 5 vol%, a Pt furnace temperature of 920 degrees C, and a reaction gas flow rate of over 200 mL/min. Absorbers were used to remove O2 and H2O from the reaction gas. The synthesis of no-carrier-added [1-11C]amino acids from [11C]HCN via [11C]aminonitriles was successfully carried out. This method is suitable for automation of [1-11C]amino acid production.

Amino Acids↗

Myocardial imaging using 11C-CoQ10 with positron emission tomography.

The potential of 11C-labeled coenzyme Q10(CoQ10) as a myocardial imaging tracer was explored with positron emission tomography (PET). Serial myocardial imaging studies were performed using 11C-CoQ10, 45Ti-diethylenetriaminepentaacetic acid (45Ti-DTPA), and 2-deoxy-2-[18F]fluoro-D-mannose (18FDM) in the same dog. Cross sectional images of the heart with 11C-CoQ10 showed relatively high radioactivity in the blood pool, when compared with images taken with 18FDM. However, when the blood spillover of radioactivity is adequately corrected with 45Ti-DTPA data, it was found that 11C-CoQ10 accumulated in the myocardium with time.

Animals↗

Positron emission tomography in minor ischemic stroke using oxygen-15 steady-state technique.

A study with positron emission tomography (PET) was performed on 10 patients with ischemic stroke and mild disability. The patients underwent cerebral angiography, x-ray computed tomography (CT) scan and regional cerebral measurements of CBF, CMRO2, oxygen extraction ratio (OER), and cerebral blood volume (CBV). Only minor arterial involvement was detected by angiography. In all patients, PET images of functional defects were more extensive than the corresponding CT hypodensity, and there were statistically significant reductions in CBF, CMRO2, and CBF/CBV ratio as compared with control subjects. Half of the regions analyzed in the affected hemisphere demonstrated a disruption of the normal coupling between CBF and CMRO2 as reflected by OER values significantly higher or lower than those of the corresponding region of the contralateral hemisphere. The pathophysiological pattern of high OER combined with a reduction in CBF proportionally greater than the reduction in CMRO2 was particularly indicative of regional chronic hemodynamic compromise in these patients.

Aged↗

Activation autoradiography: imaging and quantitative determination of endogenous and exogenous oxygen in the rat brain.

Endogenous and exogenous oxygen in the rat brain were quantitatively determined using an autoradiographic technique. The oxygen images of frozen and dried rat brain sections were obtained as 18F images by using the 16O (3He,p)18F reaction for endogenous 16O images and the 18O(p,n)18F reaction for endogenous and exogenous 18O images. These autoradiograms demonstrated the different distribution of oxygen between gray and white matter. These images also allowed differentiation of the individual structures of hippocampal formation, owing to the differing water content of the various structures. Local oxygen contents were quantitatively determined from autoradiograms of brain sections and standard sections with known oxygen contents. The estimated values were 75.6 +/- 4.6 wt% in gray matter and 72.2 +/- 4.0 wt% in white matter. The systematic error in the present method was estimated to be 4.9%.

Activation Analysis↗