Biomedical subjects

K Ishiwata

Publications and source records attributed to K Ishiwata.

At least 145 records · Page 8Linked to original sources

PubMed1990

Visualization of histamine H1 receptors in dog brain by positron emission tomography.

Histamine H1 receptors were visualized in the living dog brain using [11C]pyrilamine or [11C]doxepin by positron emission tomography (PET). The regional distribution of these carbon-11 labeled compounds in the brain corresponded well with that of the histamine H1 receptors separately determined by in vitro binding assay. The radioactivity in the brain was reduced by treatment with triprolidine (1 mg/kg), a histamine H1 antagonist. The results of our study indicate that it is feasible to visualize histamine H1 receptors in human brain using these 11C-labeled compounds and PET.

Animals↗

PubMed1990

Synthesis of omega-[18F]fluoroalkyl analogs of YM-09151-2 for the measurement of D2-dopamine receptors with PET.

Two [18F]fluoroalkyl analogs of a neuroleptic YM-09151-2 were synthesized via nucleophilic [18F]fluorination of methanesulfonyloxy- or p-toluenesulfonyloxyalkyl derivatives using no-carrier-added [18F]fluoride. Although 3-[18F]fluoropropylaminobenzamide was obtained in good yield, the yield of 2-[18F]fluoroethyl derivative was severalfold lower. The product, N-[(2RS,3RS)-1-benzyl-2-methylpyrrolidin-3-yl]-5- chloro-2-methoxy-4-(3-[18F]fluoropropyl)-aminobenzamide, was shown to have a striatum-to-cerebellum ratio comparable to that of 11C labeled YM-09151-2 and thus to be a good candidate for measuring D2-receptors in vivo.

Animals↗

PubMed1990

Tumor uptake study of 18F-labeled N-acetylneuraminic acids.

In order to develop positron-emitting tracers for imaging metabolic functions of tumors with positron emission tomography, tumor uptake of N-acetyl-3-[18F]fluoroneuraminic acid and N-acetyl-2-deoxy-2,3-di-[18F]fluoroneuraminic acid was investigated in mice or rats. The two tracers showed similar tissue distribution patterns. After i.v. injection of each tracer into mice with an FM3A tumor, the radioactivity was very rapidly cleared from normal and tumor tissues. Only tumor-to-brain and tumor-to-muscle uptake ratios were greater than 1.0 for 2 h. In 7 types of tumor models, no selective tumor uptake of tracers was observed 30 min after injection. The metabolic alteration rate of N-acetyl-3-[18F]fluoroneuraminic acid in FM3A, liver and kidney was very slow. Neither tracer may be suitable for tumor imaging in vivo.

Animals↗

PubMed1990

Ornithine decarboxylase activity in prostate and tumor: a feasibility study for PET with L-[5-14C]- and L-[5-14C]ornithine.

The aim of this study is to investigate the possibility of measuring ornithine decarboxylase (ODC) activity in tissues such as prostate and tumor, by PET. The ODC activity in vitro and the distribution of L-[1-14C]- and L-[5-14C]ornithine were studied in prostate, tumor, liver and kidney. For the animal models, rats bearing Walker 256 carcinosarcoma, were used. Our results indicate that the ODC activity in prostate is correlated with the difference in uptake between L-[1-14C]- and L-[5-14C]ornithine. Measurement of ODC activity in tumor by PET demands a tumor with an ODC activity comparable to that of prostate. Such a tumor will show a sufficient difference in uptake, which can be detected by PET.

Animals↗

PubMed1990

Specific binding of [3H]pyrilamine to histamine H1 receptors in guinea pig brain in vivo: determination of binding parameters by a kinetic four-compartment model.

The binding of [3H]pyrilamine, a selective ligand of histamine H1 receptors, to guinea pig brain in vivo was compared with its binding to a brain homogenate. The pharmacological properties (regional distribution, saturability, and stereoselectivity) of the [3H]pyrilamine binding in vivo were similar to those of the in vitro binding to brain homogenate. A dynamic four-compartment model was proposed for the analysis of the kinetics of [3H]pyrilamine binding in vivo. The receptor constants in vivo were determined by a computer-fitting method after correcting the radioactivity of arterial plasma and brain for the presence of radioactive metabolites. The in vivo association and dissociation were 213 and 42 times, respectively, slower than those of in vitro binding at 37 degrees C. A possible mechanism for slow association and dissociation in vivo is discussed.

Aminopyridines↗

PubMed1990

18F-fluoro-2'-deoxyuridine as a tracer of nucleic acid metabolism in brain tumors.

The value of 18F-fluoro-2'-deoxyuridine (18F-FUdR) as a tracer for nucleic acid metabolism was studied using an experimental rat brain-tumor model. The 18F activity in the tumor tissue 45 minutes after intravenous injection of 18F-FUdR was about 12 times higher than that in the contralateral cortex. Double-labeled autoradiography with 18F-FUdR and 14C-thymidine revealed similar brain-tumor images. In contrast, an autoradiographic comparison of 18F-FUdR with 14C-aminoisobutyric acid, which reveals the impairment of the blood-brain barrier, showed very different images. Also, the 18F radioactivity in the tumor tissue was at a constant level for 30 to 120 minutes, whereas a notable increase in 18F activity with time was observed in nucleotides and acid-insoluble fractions. These results suggest that the distribution pattern of 18F-FUdR closely correlates with the metabolism of nucleic acid and that this drug could be a useful tracer for positron emission tomography.

Animals↗

PubMed1990

Enzymatic production of L-tryptophan from DL-serine and indole by a coupled reaction of tryptophan synthase and amino acid racemase.

Enzymatic production of L-tryptophan from DL-serine and indole by a coupled reaction of tryptophan synthase and amino acid racemase was studied. The tryptophan synthase (EC 4.2.1.20) of Escherichia coli catalyzed beta-substitution reaction of L-serine into L-tryptophan and the amino acid racemase (EC 5.1.1.10) of Pseudomonas putida catalyzed the racemization of D-serine simultaneously in one reactor. Under optimal conditions established for L-tryptophan production, a large-scale production of L-tryptophan was carried out in a 200-liter reactor using intact cells of E. coli and P. putida. After 24 h of incubation with intermittent indole feeding, 110 g liter-1 of L-tryptophan was formed in molar yields of 91 and 100% for added DL-serine and indole, respectively. Continuous production of L-tryptophan was also carried out using immobilized cells of E. coli and P. putida. The maximum concentration of L-tryptophan formed was 5.2 g liter-1 (99% molar yield for indole), and the concentration decreased to 4.2 g liter-1 after continuous operation for 20 days.

Amino Acid Isomerases↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1989

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↗

PubMed1989

2-Deoxy-2-[18F]fluoro-D-galactose as an in vivo tracer for imaging galactose metabolism in tumors with positron emission tomography.

The feasibility of 2-deoxy-2-[18F]fluoro-D-galactose ([ 18F]FdGal) for imaging galactose metabolism in tumors with positron emission tomography (PET), was investigated using two hepatomas, Yoshida sarcoma, or glioma in rats, and mouse mammary carcinoma. In hepatoma-bearing rats the highest uptake of [18F]FdGal was observed in the liver followed by the kidney and tumor. The tumor uptake increased with time, and the high uptake ratios of tumor to organ were observed except for the liver and kidney. Tumor uptake was also measured in all tumors. As main metabolites in all tumors, [18F]FdGal 1-phosphate and UDP-[18F]FdGal were found by HPLC. Two hepatomas showed a slightly higher uptake and a larger percentage of UDP derivative than the other three tumors. By autoradiography the brain tumor was visualized clearly. These results indicate that [18F]FdGal has potential as a tracer for imaging galactose metabolism in tumors with PET.

Animals↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1988

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↗