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Biomedical subjects

K Ishiwata

Publications and source records attributed to K Ishiwata.

At least 127 records · Page 7Linked to original sources
PubMed1992

Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography.

While 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is a useful tumor imaging agent, its intratumoral distribution has not been described well at the cellular level. In order to demonstrate cellular localization of [18F]FDG and 2-deoxy-D-[3H]glucose (3H-DG) uptake by the tumor in vivo, C3H/He mice transplanted subcutaneously with FM3A tumors were studied 1 hr after intravenous injection of [18F]FDG or 3H-DG using micro- and macro-autoradiography. Fluorine-18-FDG and 3H-DG showed the same distribution pattern in the tumor with both autoradiographic methods. The newly formed granulation tissue around the tumor and macrophages, which were massively infiltrating the marginal areas surrounding necrotic area of the tumor showed a higher uptake of [18F]FDG than the viable tumor cells. A maximum of 29% of the glucose utilization was derived from nontumor tissue in this tumor. The comparison of double-tracer autoradiographic distribution patterns of [18F]FDG and [6-3H]-thymidine showed the differences and the similarities between glucose utilization and the DNA synthesis. Whole proliferating tissue metabolizes [18F] FDG but not vice versa. High accumulation of [18F]FDG in the tumor is believed to represent high metabolic activity of the viable tumor cells. Our results showed that one should consider not only the tumor cells proper but also the non-neoplastic cellular elements, which appear in association with growth or necrosis of the tumor cells, for precise analysis of [18F]FDG uptake in tumor-bearing subjects, especially after anti-neoplastic treatment.

Animals↗
PubMed1992

[Autoradiographic demonstration of 18F-FDG distribution within mouse FM3A tumor tissue in vivo].

To demonstrate the distribution of 2-deoxy-2-18F-fluoro-D-glucose (FDG) within the tumor in vivo, C3H/He mice transplanted with FM3A tumors were studied one hour after intravenous injection of FDG using whole-body, macro- and micro-autoradiography. The whole-body autoradiograph showed that the tumor mass as well as the brain, heart, bone marrows, and the diaphragm and crus diaphragm were clearly visualized. The macro-autoradiograph showed the heterogeneous distribution of FDG in the tumor mass. Markedly dense areas surrounding the tumor and the necrotic area were observed. Micro-autoradiograph showed the high grain densities in the macrophages between the necrosis and viable tumor cells, and in the young granulation tissues demarcating between the tumor and surrounding intact host tissues. Our results showed that the FDG uptake in the tumors may reflect not only the uptake by the tumor cells but also that by the inflammatory reaction elements.

Animals↗
PubMed1991

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

The routine measurement of L-[methyl-11C]methionine in human plasma after i.v. injection of the tracer is described. The protein-free plasma metabolites of the tracer were analyzed using a cation-exchange column (Aminex A-6) eluted with a pH 4.25 citrate buffer. The ratios of L-[methyl-11C]methionine for the total radioactivity decreased gradually, and the standard deviations among 19 humans were relatively small for 30 min: 97.2 +/- 1.4%, 5 min; 92.6 +/- 2.1%, 10 min; 89.4 +/- 4.0%, 15 min; 84.1 +/- 3.1%, 20 min; 73.1 +/- 9.8%, 30 min; 45.0 +/- 16.8%, 60 min. A convenient analysis using a Bond elute SCX cartridge showed slightly larger ratios than those measured by liquid chromatography.

Adolescent↗
PubMed1991

Synthesis and radiation dosimetry of 4-borono-2-[18F]fluoro-D,L-phenylalanine: a target compound for PET and boron neutron capture therapy.

The 18F-labeling of 4-borono-D-L-phenylalanine (BPA), a potential target compound for cancer treatment with boron neutron capture therapy, is described. By direct fluorination of BPA with [18F]AcOF or [18F]F2 followed by HPLC separation, 4-borono-2-[18F]fluoro-D,L-phenylalanine was prepared with radiochemical yields of 25-35% and with a radiochemical purity of over 99%. The tissue distribution study showed that the compound has potential as a tracer for pancreas imaging with positron emission tomography. Radiation dosimetry is also described.

Animals↗
PubMed1991

Potential radiopharmaceuticals labeled with titanium-45.

The potential of some compounds labeled with cyclotron-produced titanium-45 (45Ti) as radiopharmaceuticals was studied. Properties of colloid formation of 45TiOCl2 or 45TiO-phytate in vivo resulted in the highest radioactivity uptake in the rat liver, followed by the spleen, suggesting potential for imaging the reticuloendothelial system. Three 45TiO-complexes with diethylenetriaminepentaacetic acid, citric acid and human serum albumin showed the highest radioactivity levels in the blood over 6 h. The binding of the 45Ti with plasma transferrin in vitro and in vivo suggested that these compounds can be used for estimating the blood volume. Also, potential as an indicator representing the breakdown of the blood-brain barrier in the rat was demonstrated by autoradiography.

Animals↗
PubMed1991

4-Borono-2-[18F]fluoro-D,L-phenylalanine as a target compound for boron neutron capture therapy: tumor imaging potential with positron emission tomography.

We studied the tumor uptake and metabolism of 4-borono-2-[18F]fluoro-D,L-phenylalanine ([18F]FBPA), an 18F-labeled target compound for boron neutron capture therapy. In mice bearing FM3A mammary carcinoma, the accumulation of [18F]FBPA in the FM3A for the first 2 h, and its decrease in all other tissues, resulted in high FM3A-to-tissue uptake ratios. In the FM3A, the tracer was stable for metabolic alteration, which was in contrast to the gradual increase of protein-bound radioactivity in plasma. Imaging of FM3A was demonstrated by whole body autoradiography. [18F]FBPA has potential for use as a PET tracer for tumor imaging with high contrast, even in the pancreas.

Animals↗
PubMed1991

Possibility for tumor detection with fatty acid analogs.

Newly synthesized 17-[18F]fluoro-3-methylheptadecanoic acid ([18F]BMHDA), 16-[18F]fluoropalmitic acid ([18F]PA) and 15-(p-[125I]iodophenyl)-3-R,S-methylpentadecanoic acid ([125I]BMIPP), fatty acid tracers, were examined for the possibility of tumor imaging using 10 tumor models in rats and mice. The highest tumor/muscle ratios with [18F]BMHDA were 2.3 using rat tumor AH109A and 1.9 using mouse tumor B16F1 (tumor accumulation 0.41 +/- 0.05, 4.29 +/- 0.77% ID/g, respectively). Tumor/muscle ratios with [125I]BMIPP and [18F]PA were lower than those with [18F]BMHDA. Labeled fatty acids seem to have a lower potential for tumor detection.

Animals↗
PubMed1991

A comparative PET study using different 11C-labelled amino acids in Walker 256 carcinosarcoma-bearing rats.

In Walker 256 carcinosarcoma-bearing rats, the dynamic distribution of L-[1-11C]tyrosine, L-[methyl-11C]methionine, L-[1-11C]methionine and D-[1-11C]methionine has been measured by PET. An equivalent tumor-imaging potential was observed for each of the three L-amino acids. Thirty minutes after injection, the tumors accumulated 57% (P less than 0.01) more 11C-activity from L-[1-11C]methionine than from L-[methyl-11C]methionine. At the same point of time, the livers showed a 33% (P less than 0.001) higher 11C-uptake with L-[methyl-11C]methionine than with L-[1-11C]methionine. The dynamic tissue data are in agreement with the findings in experiments with 14C-analogs.

Amino Acids↗
PubMed1991

Metabolic fates of 2'-deoxy-5-[18F]fluorouridine in tumor-bearing mice and human plasma.

The metabolic fate of 2'-deoxy-5-[18F]fluorouridine ([18F]FdUrd), a useful positron emission tomography (PET) tracer of nucleic acid metabolism in tumors, was investigated in mice and humans. A rapid increase in labeled catabolites was found in mouse and human plasma. In mouse FM3A mammary carcinoma, the corresponding catabolites were also detected in addition to metabolites which were activated by the nucleic acid metabolism. From a biodistribution study of beta-[3H]alanine, alpha-[18F]fluoro-beta-alanine, a major catabolite, was assumed to be taken up twice as much by tumor than by the brain. Nucleic acid metabolism in brain tumors by [18F]FdUrd-PET may be assessed using normal brain regions as a reference.

Animals↗
PubMed1991

Absorbed dose estimates in positron emission tomography studies based on the administration of 18F-labeled radiopharmaceuticals.

Absorbed doses were estimated after intravenous administration of 18F-labeled radiopharmaceuticals in Positron Emission Tomography (PET) studies. These radiopharmaceuticals, [18F]-2-Fluoro-2-Deoxy-D-Glucose (FDG), 6-[18F]Fluoro-L-Dopa (FDOPA) and 18F-5-Fluorodeoxyuridine (FdUR), are used in clinical research at the Cyclotron and Radioisotope Center of Tohoku University. Radiopharmaceutical biokinetic values were measured in humans or extrapolated from animal experiments. Selective organ uptake and rapid clearance of activity from the blood were observed. High activity in the bladder contents of humans was found. Calculations were made by the MIRD method, modified to account for the differences in physique and organ mass between the Caucasian Reference Man and the Japanese one. The bladder wall receives the highest dose (more than 1.23 x 10(-1) mGy/MBq) when any of these compounds are administered. Other organs receiving high doses are the heart, brain and kidneys from FDG; the kidneys and pancreas from FDOPA, and the kidneys and small intestine from FdUR. These organs received absorbed doses of more than 2.7 x 10(-2) mGy/MBq. Effective dose equivalents of 2.4 x 10(-2), 2.6 x 10(-2) and 3.3 x 10(-2) mSv/MBq were estimated in the intravenous administration of 18F-FDG, 18F-FDOPA and 18F-FdUR, respectively.

Adult↗
PubMed1991

Measurement of D2 dopamine receptor-specific carbon-11-YM-09151-2 binding in the canine brain by PET: importance of partial volume correction.

Carbon-11-YM-09151-2 binds highly selectively to D2 dopamine receptors in the brain. Using this ligand, D2 dopamine receptor density (Bmax) and affinity (Kd) in canine striatum were measured. After administering various doses of the ligand in nine experiments, regional uptake was followed by repeated PET scanning for up to 80 min. D2 dopamine receptor specific binding at equilibrium was defined as striatal minus occipital activity after partial volume correction. Bmax and Kd were estimated by Scatchard analysis to be 40.3 pmole/ml of tissue and 22.9 nM, respectively. When a low mass dose of the ligand was administered, the bound-to-free ligand ratio in the striatum at equilibrium was consistent with the Bmax/Kd value obtained from the Scatchard analysis. The present study demonstrates the importance of partial volume correction and the Bmax/Kd measurement in a single PET study with carbon-11-YM-09151-2.

Animals↗
PubMed1991

Phenotypic changes in hepatic mast cells accumulating around the metacestodes of Taenia taeniaeformis in rats.

Staining properties, kinetics and degranulation of the hepatic mast cells (HMC) accumulating around the metacestodes of Taenia taeniaeformis in the liver of rats were studied. Two different types of HMC, designated as Type I and Type II, could be classified according to histochemical properties and response to compound 48/80. Type I cells resembled mucosal mast cells (MMC), whereas Type II did not. HMC, mostly Type I, were observed from day 14 postinfection (PI), while Type II were seen only from day 28 PI. On day 28 PI, Type II represented a transitional staining pattern between MMC and connective tissue mast cells (CTMC). The ratio of Type II to Type I increased gradually with the course of infection and was about 1 to 1 on day 70 PI. At this time, most of the HMC that constituted Type II as well as CTMC could be stained with berberine sulfate. While the phenotypic change of HMC to CTMC was found in the middle and inner capsular layers, most of the HMC in the outer capsular layer maintained the phenotype of MMC. The present results suggest that hepatic mast cells increased as the MMC phenotype, then showed the heterogeneity in which the transitional form of mast cells emerged followed by the appearance of the CTMC type.

Animals↗
PubMed1991

Laboratory rodent models for the tapeworm-stage of Taenia saginata and other related taeniid species.

Attempts were carried out to establish alternative definitive host systems for Taenia saginata, T. crassiceps, T. hydatigena, Echinococcus multilocularis and E. granulosus, in rodents. Following oral inoculation of cysticerci or protoscoleces, the tapeworm-stage development and sexual maturation of the 5 taeniid species in the intestine of a golden hamster (GH) and Mongolian gerbil (MG), both treated with prednisolone, were examined. Sexually mature T. saginata tapeworms were recovered from MG pretreated with prednisolone. The life cycles of E. multilocularis can be completed in MG and T. crassiceps in both MG and GH. T. hydatigena and E. granulosus developed to a certain extent at the tapeworm stage in MG pretreated with prednisolone. Potential use of rodents as an alternative definitive host for taeniid species is discussed.

Animals↗
PubMed1991

Tracer feasibility for monitoring tumor radiotherapy: a quadruple tracer study with fluorine-18-fluorodeoxyglucose or fluorine-18-fluorodeoxyuridine, L-[methyl-14C]methionine, [6-3H]thymidine, and gallium-67.

In a rat AH109A tumor model, metabolic tracers for glucose, amino acid, and nucleic acid metabolisms (2-deoxy-2-[18F]fluoro-D-glucose (18FDG), L-[methyl-14C]methionine (14C-Met), [6-3H]thymidine (3H-Thd), and 2'-deoxy-5-[18F]fluorouridine (18FdUrd], and the conventional radionuclide 67Ga-citrate were used to assess the feasibility of monitoring tumor radiotherapy using a quadruple tracer technique. Two combinations of four tracers (18FDG or 18FdUrd, 14C-Met, 3H-Thd and 67Ga) were compared in a time-course study after single-dose irradiation (20 Gy) and were also used in a dose-dependency study performed 6 days after 5, 10, 15, or 20 Gy of irradiation. Fluorine-18-FDG showed a large change in uptake and a steady response to radiotherapy. Fluorodeoxyuridine showed a rapid decrease after radiotherapy, but the range of change in uptake was narrow. Gallium-67 could not detect tumor response early after treatment, but showed a marked change in uptake later. [6-3H]Thd and 14C-Met showed a rapid response to irradiation and a high sensitivity for monitoring radiotherapy, suggesting that they may be feasible for PET studies.

Animals↗
PubMed1991

Selective 2-[18F]fluorodopa uptake for melanogenesis in murine metastatic melanomas.

The relationship between 3,4-dihydroxy-2-[18F]fluoro-L-phenylalanine (2-[18F]FDOPA) uptake and melanogenesis was studied using mice bearing two B16 melanomas: B16-F1 has a higher melanin synthesis ability and a slower growing rate than the higher metastatic B16-F10. A significantly higher 2-[18F]FDOPA uptake by B16-F1 than by B16-F10 and a reverse relationship for the uptake of [14C] 2-deoxy-2-fluoro-D-glucose and [3H]thymidine were observed 1 hr postinjection. F1-to-F10 ratios of both the 2-[18F]FDOPA uptake and the acid-insoluble radioactivity increased to about 5 at 6 hr, which paralleled the melanin content. FM3A mammary carcinoma showed a 2-[18F]FDOPA uptake similar to the B16-F10 but without the acid-insoluble radioactivity. With D,L-DOPA loading, a 55% decreased uptake by FM3A 1 hr postinjection was significantly greater than the 20% reduction in both melanomas. O-Methylated 2-[18F]FDOPA was a predominant acid-soluble metabolite in all tumors. Whole-body autoradiography discriminated the two melanomas clearly. 2-[18F]FDOPA may be a promising tracer for the selective imaging of melanogenesis.

Animals↗
PubMed1990

Localization of [18F]fluorodeoxyglucose in mouse brain neurons with micro-autoradiography.

This is the first study of micro-autoradiography (micro-ARG) for [18F]2-fluoro-2-deoxy-D-glucose [( 18F]FDG). The localization of [18F]FDG was demonstrated in dendrites of neuron and also in the myelinated axon in mouse normal brain in vivo. The nucleolus was relatively free of label. The counted silver grain numbers in autoradiogram were linearly correlated to the 18F radioactivities in the specimen. The micro-ARG using positron emitting 18F is a very time-saving technique with 4 hours exposure compared with the conventional method using 3H- or 14C-labeled tracers.

Animals↗