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Biomedical subjects

R Iwata

Publications and source records attributed to R Iwata.

At least 91 records · Page 5Linked to original sources

N-[18F]fluoroacetyl-D-glucosamine: a potential agent for cancer diagnosis.

Positron labeled substrates such as sugars, amino acids, and nucleosides have been investigated for the in-vivo evaluation of biochemical processes in cancerous tissue. Hexosamines are obligatory structural components of many biologically important macromolecules, including membrane glycoproteins and mucopolysaccharide. We evaluated a new synthesized pharmaceutical, N-[18F]fluoroacetyl-D-glucosamine (18F-FAG), which is a structural analog of N-acetyl-D-glucosamine. C3H/HeMsNRS mice bearing spontaneous hepatomas were used for the tissue distribution study. At 60 min after injection, high uptakes were found in tumor (5.16, mean value of %dose/g), liver (3.71), and kidney (3.27). The tumor uptake of 18F-FAG showed the highest value in all tissue. In the PET study, VX-2 carcinoma of the rabbit was clearly visualized. Our preliminary results suggest that 18F-FAG has potential as a new agent for tumor imaging.

Acetylglucosamine↗

Differential diagnosis of lung tumor with positron emission tomography: a prospective study.

To predict the nature of non-calcifying lung tumors, we performed a prospective study of 46 cases with L-[methyl 11C]methionine (MET, 24 cases) and 18F-fluorodeoxyglucose (FDG, 22 cases) using positron emission tomography (PET). Mean tumor/muscle radioactivity ratios are 5.3 +/- 2.0 (n = 14) for malignant and 1.9 +/- 0.9 (n = 10) for benign with MET (p less than 0.001), and 4.4 +/- 2.2 (n = 12) and 1.5 +/- 0.3 (n = 10), respectively, with FDG (p less than 0.001). The ratios indicate that malignant tumors have higher metabolic demand than benign lesions. Tumors less than 1 cm in diameter were difficult to accurately evaluate due to PET resolution. Compared to the diagnosis at pathology, the MET study showed a sensitivity of 93% (13/14), a specificity of 60% (6/10), and an accuracy of 79% (19/24). The FDG study showed 83% (10/12), 90% (9/10), 86% (19/22), respectively. No significant differences were observed between the two tracers. This study suggests that PET studies using either MET or FDG may be very useful for the differential diagnosis of lung tumors.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

Impact of routine inquiry legislation in Oregon on eye donations.

Routine inquiry legislation can significantly affect procurement of donor eye tissues. Oregon Revised Statute (ORS) 97.268 was the first legislation of this type passed in the United States. In the first 12 months under this legislation, the Oregon Lions Eye Bank obtained, 2,312 eyes, sustaining a 135% increase in donor eye procurement over the yearly average for 1984-1985. During the first 12 months of routine inquiry, 484 corneas suitable for penetrating keratoplasty were obtained versus an annual average of 291 corneas for 1984-1985. Tissues for other transplant purposes and for research have similarly become more available. Age of donor tissue appears to be increasing slightly due to the disproportionate increase of donor eyes from the 70-or-over population. The Oregon Donor Program, the public and professional education coalition of the transplant programs in the state of Oregon, has played an invaluable role in making this penalty-free law a success.

Corneal Transplantation↗

Simplified enzymatic synthesis and biodistribution of 11C-S-adenosyl-L-methionine.

11C-S-Adenosyl-L-methionine (11C-SAM) was synthesized enzymatically from 11C-L-methionine using rat-liver extract [40%-50% saturated (NH4)2SO4 fraction] as the enzyme source. In biodistribution studies in rats, the highest uptake of 11C-SAM was found in the kidneys. 11C-SAM was also accumulated in the small intestine, pancreas, adrenal gland, liver, and spleen. The uptake of 11C-SAM in the brain increased with time, but remained low. At 30 min after injection, about 50%-60% of the 11C radioactivity was present in the acid-insoluble fraction of the kidneys and liver. When a high loading dose of 11C-SAM was administered, the kidney uptake was enhanced, but the proportion of the radioactivity present in the acid-insoluble fraction was lower. In a study of one rabbit, the kidney uptake was of 11-SAM clearly visualized using positron-emission tomography.

Animals↗

In vivo kinetics and displacement study of a carbon-11-labeled hallucinogen, N,N-[11C]dimethyltryptamine.

The endogenous hallucinogen, N,N-dimethyltryptamine (DMT), was labeled with carbon-11 and its regional distribution in rat brain studied. [11C]DMT showed higher accumulation in the cerebral cortex, caudate putamen, and amygdaloid nuclei. Studies of the subcellular distribution of [11C]DMT revealed the specific localization in the fractions enriched with serotonin receptors only when a very low dose was injected into rats. The proportions of the radioactivity in receptor-rich fractions were greatly enhanced by pretreatment with the monoamine oxidase inhibitor, pargyline. Specific binding of [11C]DMT to serotonin receptors in dog brain was demonstrated by a positron emission tomographic study in which 5-methoxy-N,N-dimethyltryptamine caused approximately 20% displacement of the radioligand from the receptors.

Animals↗