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Biomedical subjects

T Ido

Publications and source records attributed to T Ido.

At least 163 records · Page 9Linked to original sources

6-[18F]fluoro-L-fucose: a possible tracer for assessing glycoconjugate synthesis in tumors with positron emission tomography.

The potential of 6-[18F]fluoro-L-fucose (6-[18F]FFuc) for assessing glycoconjugate synthesis in tumors with positron emission tomography (PET) was investigated. Using the tissue sampling method with five tumor models, different time-radioactivity profiles were found: a nearly constant level in Lewis lung carcinoma (3LL) and different clearance patterns in others. Rapid clearance in normal tissues resulted in preferable uptake ratios for tumor imaging of brain and pancreas. Metabolic studies and the L-fucose loading effects on the tissue uptake proved the tracer to be a biochemically active L-fucose analog. Imaging of the intracranial rat glioma and 3LL in lungs or hepatomas in mice by autoradiography (ARG) and intramuscular VX-2 carcinoma in rabbits by PET was demonstrated. Using double-radionuclide ARG, similar distribution images of 6-[18F]FFuc and 14C-L-fucose but different tumor-to-liver uptake ratios were found. A metastasis model seemed to show a higher uptake of both tracers as compared to a primary tumor model.

Animals↗

Imaging of water distribution in the rat brain by activation autoradiography.

Regional water distribution in the rat brain was obtained autoradiographically by activation analysis. The autoradiogram obtained for the normal rat brain showed high accumulation of water in the areas of sensory-motor cortex, hippocampus, thalamus, and amygdaloid cortex, whereas corpus callosum and internal capsule showed low water contents as expected. The estimated values of water content were 78.6 +/- 4.9 weight % for gray matter, and 73.5 +/- 4.9 weight % for white matter, respectively. The mean values of the water content were consistent with those obtained by a conventional drying-weighing method.

Animals↗

Metabolic fate of L-[methyl-11C]methionine in human plasma.

The metabolites of L-[methyl-11C]methionine in the plasma of 8 patients with tumors were measured for 60 min after injection. In the plasma, after a rapid clearance, the total radioactivity remained constant, and protein-bound radioactivity increased rapidly. Non protein metabolites detected by HPLC as at least two components besides methionine, increased with time. Significant individual variations for the metabolism were observed. At 60 min after injection, 36.5% (range: 16%-72%) and 45.3% (range: 13%-74%) of the 11C was measured as methionine and labeled proteins, respectively.

Adolescent↗

Preparation of a fine powder of 2-deoxy-2-[18F]fluoro-D-glucose suitable for inhalation to diagnose lung diseases by means of PET.

Fine 2-deoxy-2-[18F]fluoro-D-glucose (18FDG) powder was obtained by adding diethyl ether into a methyl alcohol solution of 18FDG and other sugar as seed. When micronized particles of sodium N-acetyl-neuraminate (Neu5Ac-Na) were used as seed crystals, particles containing 18FDG were obtained and 80% of them were smaller than 10 microns in size. More than 60% of these crystals were 4-6 microns in size. In a preclinical study of forced inhalation in a dog, the 18FDG fine powder was mainly distributed in the trachea. The radioactivity in the trachea then increased once and a gradual decrease followed. The radioactivity was transferred into the blood and radioactivity incorporation into the heart was observed. After a normal volunteer inhaled 18FDG dry powder aerosol, the radioactivity was found in the respiratory tract and the peripheral area of the lung by means of PET. Absorption and in vivo dynamics of the 18FDG were also analysed.

Administration, Inhalation↗

Feasibility study of fluorine-18 labeled dopa for melanoma imaging.

Feasibility of fluorine-18 labeled L-dopa for melanoma imaging was investigated. In B16 melanoma-bearing mice given 2-[18F]fluoro-L-dopa, the radioactivity in the B16 decreased for the first 60 min and then remained constant, while all other tissues investigated decreased with time. High tumor uptake ratios for all other tissues except for the pancreas were obtained at 120 min. 6-[18F]Fluoro-L-dopa showed a similar tissue distribution. However, the B16 uptake was about half that value for the 2-fluoro analogue. A higher incorporation rate of 2-[18F]fluoro-L-dopa into the acid-precipitable fraction of the melanoma also showed that the 2-[18F]fluoro-L-dopa was a preferable melanin precursor. Among the four kinds of non-melanoma tumors in mice or rats three tumors showed an uptake of 2-[18F]fluoro-L-dopa similar to the B16 at 60 min. However, larger melanoma-to-tissue uptake ratios were observed when compared to non-melanoma tumors.

Animals↗

In vivo assessment of 6-deoxy-6-[18F]fluoro-D-galactose as a PET tracer for studying galactose metabolism.

The potential of 6-deoxy-6-[18F]fluoro-D-galactose (6-[18F]FdGal) as an in vivo tracer for studying galactose metabolism in tumors and liver was investigated. High uptake and rapid clearance of the radioactivity were observed in many organs of mice after i.v. injection of the tracer. D-Galactose loading did not affect liver uptake. Three experimental tumors showed a slightly higher uptake than other tissues, and rat brain tumor was clearly visualized by autoradiography. However, the radioactivity in tumors decreased rapidly. In the liver, a significant amount of the tracer was found in a galactonate form, while this oxidation was a minor metabolic pathway in the tumors. In both tumor and liver tissues, small amounts of the tracer were incorporated into macromolecular glycoconjugate via phosphate and uridylate forms as intermediate precursors. These results indicate that 6-[18F]FdGal is not suitable for studying galactose metabolism in vivo because of the low affinity of the tracer for the metabolism.

Animals↗

Localizing efficiency of [48V]vanadyl-pheophorbide in tumor as a new tumor imaging agent.

[48V]vanadyl-pheophorbide (48V-Pheo) was synthesized by insertion of 48V into pheophorbide (Pheo), a decomposition product from chlorophyll. At 24 h after injection, 48V-Pheo showed a clearer image of an FM3A tumor than inorganic 48V. This agent also accumulated in MH 134 and S 180 tumors as well as in FM3A tumors. The imaging efficiency was dependent on the affinity of Pheo for tumors. 48V-Pheo seems to be suitable as a tumor imaging agent in conjunction with photodynamic therapy.

Animals↗

Kinetic evaluation of 11C-1-aminocyclopentane carboxylic acid in rabbits bearing VX-2 tumors using positron emission tomography.

Tumor detection with 11C-1-aminocyclopentane carboxylic acid (11C-ACPC) showed that this amino acid has a high affinity for malignant tumors. We studied the kinetics of intravenously injected 11C-ACPC in the rabbit VX-2 tumor using positron emission tomography. Three female rabbits bearing VX-2 tumor in the thighs were used. High uptake of 11C-ACPC was seen in the tumor and liver. 11C-ACPC in plasma decreased rapidly after injection and its activity in the tumor increased with time. The kinetic evaluation of ACPC uptake into the tumor was performed using the unidirectional transport model. The average values of the transfer constant of 11C-ACPC for VX-2 tumor were 0.030 +/- 0.002 ml/min/g. This preliminary result may form the basis for a quantitative analysis of the in vivo distribution of 11C-labeled ACPC in tumors.

Amino Acids↗

Differential diagnosis of AH109A tumor and inflammation by radioscintigraphy with L-[methyl-11C]methionine.

For the evaluation of tumor imaging with L-[methyl-11C]methionine (11C-Met), a basic study on the differentiation of tumor from inflammation with 11C-Met and a comparison of the diagnostic value of the image with that obtained using 67Ga citrate, a conventional scintigraphic agent, are important. 11C-Met accumulations into inflammatory lesions, AH109A tumor and normal tissues of rats were examined by means of a tissue distribution study. Aseptic inflammatory lesions on the back of Donryu rats induced by croton oil and 1.5% carrageenan showed significantly lower accumulations of 11C-Met than the AH109A tumor. Histologically, croton oil induced granulomatous inflammation and carrageenan, acute exudative inflammation. Whole-body autoradiography with 14C-Met, a substitute for 11C-Met, was negative in the carrageenan lesion and showed a slightly increased activity at the periphery of the croton oil lesion, in contrast with the high tumor activity. Whole-body autoradiography with 67Ga citrate was performed to compare the imaging ability with that of 14C-Met; it showed high activities in the tumor, bone, and intestine, and a broad increased activity at the periphery of the croton oil lesion, but was negative in the carrageenan lesion. 11C-Met accumulations in the inflammations were very low and clinical application with positron emission tomography, should be useful for the differential diagnosis of tumor from inflammation.

Animals↗

Synthesis of C-labeled imipramine and its biodistribution in mice: a potential tracer for positron emission tomography.

A tricyclic antidepressant, C-labeled imipramine was synthesized by N-methylation of desipramine with 11CH3I to assist in the imaging of the human imipramine receptor by positron emission tomography. The radiochemical yield after purification of 11C-imipramine by high performance liquid chromatography was 28-63% at a specific activity of 26-53 Ci/mmol. The time required for synthesis, including purification was 30 min from the end of 11CH3I trapping. The organ distribution of 11C-imipramine was investigated in mice at various times after i.v. injection. The main accumulation of radioactivity was in the kidney, followed by the lung and the heart. In the brain, the radioactivity levels in the hypothalamus and striatum were the highest and remained constant, differentiating them from other portions of the brain. Furthermore, the result of a binding assay with 3H-labeled imipramine suggested that the regional distribution of 11C-imipramine in the same mouse brain correlated to that of the high affinity imipramine binding site.

Animals↗

Computed tomography, magnetic resonance imaging, positron emission tomography and evoked potentials at early stage of adrenoleukodystrophy.

An 8 year-old-boy with adrenoleukodystrophy (ALD) was subject to an x-ray computed tomography (CT) scan, magnetic resonance imaging (MRI), positron emission tomography (PET) using 18F-fluorodeoxy glucose and evoked potential studies, about 3 months after the onset of neurologic symptoms. A CT showed decreased radiodensity over the white matter of both occipital lobes, and high density areas on the periventricular space. No contrast enhancement was observed around the low dense white matter, while occipital grey matter seemed to be almost normal. MRI demonstrated a larger and more obvious lesion of prolonged T2 relaxation time which was 170-250 msec than that detected by CT scan. The PET demonstrated wide and severe hypometabolism for glucose over the grey and the white matter of bilateral occipital lobes. The visual evoked potential (VEP) was scarcely elicitable, while the auditory brainstem response (ABR) and short latency somatosensory evoked potential (SSEP) was normal. These imaging studies suggest that extensive and profound demyelination exists in the occipital white matter. For detection of demyelinizing process, MRI may be more effective than CT in this disorder. The PET study revealed that there may have been an abnormality of the grey matter as well as the white matter in the occipital lobe. The VEP disappeared in the relatively early stage. The brainstem may not be involved at such early stage in light of normal ABR and SSEP.

Adrenoleukodystrophy↗

[Double tracer whole body autoradiography using a short-lived positron emitter and a long-lived beta emitter].

We investigated glucose and amino acid metabolism in tumors and other organs using whole body autoradiography with a short-lived positron emitter and a long-lived beta emitter. The radioactive compounds used were 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) with a half life of 109.8 min and L-[methyl-14C]-methionine (14C-MET) with a half life of 5,730 years. A Donryu rat weighing about 150 g was subcutaneously inoculated at the back with experimental tumors of AH109A and AH272. 74 MBq (2 mCi) of 18F-FDG and 740 kBq (20 microCi) of 14C-MET was administered and after 30 min, the rat was sacrificed. Whole body frozen sections were obtained using autocryotome. For the 18F-FDG autoradiogram, the frozen sections were exposed to an X-ray film for 6 h. After seven days, these frozen sections were again exposed to 14C-MET for a week. Cross-contamination was minimized by adjusting the exposure time, the interval of exposures and the administered dose. The accumulation of the tracers was represented as the optical density ratio of the tissue of interest to the muscle. The tumor ratios were 12.5 for 18F-FDG and 8.6 for 14C-MET showing the highest accumulation in the whole body autoradiogram. In contrast the inflammatory tissue ratios were 1.27 for 18F-FDG and 0.77 for 14C-MET showing very low amino acid metabolism. With the present double tracer whole body autoradiogram, 18F-FDG accumulation was seen in the brain and the heart but not to the liver as against 14C-MET accumulation which was seen to the liver but not to the brain and the heart.

Animals↗

D2-dopamine receptor specific brain uptake of carbon-11-labeled YM-09151-2.

The in vivo D2-receptor specific brain uptake of N-[(2RS,3RS)-1-benzyl-2- methyl-3-pyrrolidinyl]-5-chloro-2-methoxy-4-[11C]methylaminobenzamide ([11C]YM-09151-2), was investigated. In rat brain the high uptake of [11C]YM-09151-2 in striatum was displaced with sulpiride, spiroperidol, and YM-09151-2. SCH-23390 and ritanserin, D1-dopamine and S2-serotonin antagonists, showed no effect on the distribution of [11C]YM-09151-2. In the striatum at 60 min, 95% of the radioactivity was detected as [11C]YM-09151-2 by high performance liquid chromatography. On the other hand, 41% of 11C in the plasma at 60 min was observed as metabolites. In vivo autoradiography showed a high uptake of [11C]YM-09151-2 in the striatum and in the nucleus accumbens of rat brain. A high uptake of radioactivity was also found in the canine basal ganglia with positron emission tomography. The uptake was reduced by pretreatment with spiroperidol. The present results demonstrate that [11C]YM-09151-2 is a D2 receptor specific compound and is a potential in vivo tracer for measuring D2 receptors.

Animals↗

Rapid and sensitive response of carbon-11-L-methionine tumor uptake to irradiation.

Evaluation of cancer treatments by the measurement of tumor size is an unsatisfactory method for the observation of the radiobiologic response of the tumor. After 20 Gy single-dose irradiation of 60Co to rat tumor AH109A, the L-[methyl-11C] methionine tumor uptake, the microscopic extension of tumor necrosis and the shrinkage of tumor were compared quantitatively. L-[Methyl-11C]methionine uptake fell to 54 +/- 19% of non irradiated tumor at 12 hr after irradiation. Necrosis extended 49 +/- 7% of total tissue volume after 3 days. Tumor volume decreased 48 +/- 12% 10 days after irradiation. L-[Methyl-11C]methionine uptake by tumor showed a sharp and rapid linear decrease after irradiation and the response of the uptake to irradiation preceded the extension of necrosis and tumor shrinkage. We conclude that radiation effect on the tumor may be evaluated immediately after irradiation by the measurement of L-[methyl-11C]methionine uptake and thus clinical application of positron emission tomography may give a benefit to the patients undergoing radiotherapy.

Animals↗

[Computerized digital image analysis of optic nerve heads with a three-dimensional image analyzer, IMAGEnet and a comparison with the Optic Nerve Head Analyzer].

Computerized digital image analysis of the optic nerve heads of 17 eyes with various sizes of optic disc cupping was performed using two kinds of three dimensional image analyzers, the IMAGEnet and the Optic Nerve Head Analyzer (ONHA). Intraphotographic error variances of measurements with both instruments were evaluated by measuring each image of the optic discs twice. The mean coefficient of variation (CV) with the IMAGEnet for the vertical cup/disc ratio, the horizontal cup/disc ratio, the cup volume, the rim area, and the rim area/disc area ratio were 3.75%, 3.03%, 7.89%, 2.55% and 1.36%, respectively. With the ONHA, the mean CV for the total cup/disc ratio, the cup volume, the rim area, and the rim area/disc area ratio were 0.82%, 0.21%, 2.39%, and 1.56%, respectively. The value of the cup/disc ratio and the cup volume obtained by the IMAGEnet was smaller than those by the ONHA (p greater than 0.1). Conversely, the rim area and rim area/disc area ratio measured by the IMAGEnet were statistically significantly larger than those by the ONHA (p = 0.01). Statistically significantly positive correlation was demonstrated for measurements made by both instruments in all disc parameters (p less than 0.01). These results seem to indicate the high reliability of the two instruments, however, further investigation is needed for the evaluation of the accuracy of measurements.

Glaucoma↗

Quantitative evaluation of L-[methyl-C-11] methionine uptake in tumor using positron emission tomography.

Tumor uptake of L-[methyl-11C]methionine ([11C]Met) was assessed in six patients with brain tumors and three patients with lung cancer using positron emission tomography (PET). In arterial plasma samples taken at 5, 15, 30, and 60 min after injection, a fraction of [11C]Met was measured using high performance liquid chromatography in individual patients. Employing curve fitting, a history of [11C]Met activity was obtained as an input function. By means of sequential PET scannings and graphic analysis, uptake rate and distribution volume of [11C]Met in tumor tissue were calculated. In two studies irreversible uptake into the tumors was not seen when total plasma 11C activity was used as the input; however when [11C]Met plasma activity was used, definite irreversible uptake was seen, indicating tumor viability. In other studies, up to 24% underestimation of uptake rate was found. The present results demonstrated the importance of measuring [11C]Met in plasma for quantitative assessment of in vivo amino acid metabolism in tumors.

Adolescent↗