Biomedical subjects

K Ishiwata

Publications and source records attributed to K Ishiwata.

At least 91 records · Page 5Linked to original sources

PubMed1996

Feasibility of fluorine-18-fluorophenylalanine for tumor imaging compared with carbon-11-L-methionine.

UNLABELLED: L-[methyl-11C]methionine (11C-Met) is a useful tracer for tumor imaging with PET. The drawbacks include a short half-life and high physiological accumulation in abdominal organs. To overcome these shortfalls, the feasible use of [18F]fluorophenylalanine (18F-Phe), which shares the same amino acid transport system with Met, for tumor imaging was examined. METHODS: The time course of tissue distribution of 18F-Phe and the tumor uptake response to radiotherapy were compared with 14C-Met and [3H] thymidine (3H-Thd) in the rat AH109A tumor model. Intratumoral distribution of 18F-Phe was compared with 14C-Met and 14C-Thd using double-tracer macroautoradiography (ARG). We also evaluated whole-body ARG. RESULTS: Tumor uptake of 18F-Phe peaked at 60 min postinjection and was higher than that of the liver, intestine and kidney but lower than the pancreas. Tumor uptake of 18F-Phe was similar to that of 14C-Met. Tumor-to-blood and tumor-to-muscle ratios were higher in 14C-Met compared with that of 18F-Phe because of the rapid blood clearance of 14C-Met. With whole-body ARG, the tumor was clearly visualized with high contrast. Radiotherapeutic response of tumor uptake of 18F-Phe was as rapid as that with 14C-Met and with 3H-Thd. Intratumoral distribution of 18F-Phe and 14C-Met were identical, and 18F-Phe and 14C-Thd were similar. CONCLUSION: Fluorine-18-Phe seems to be a potentially useful amino acid tracer for tumor imaging with a longer half-life than 11C, with higher tumor contrast in the abdomen than Met and a similar sensitive response to radiotherapy.

Animals↗

PubMed1996

Carbon-11-labeled KF15372: a potential central nervous system adenosine A1 receptor ligand.

UNLABELLED: The carbon-11-labeled selective adenosine A1 antagonist KF15372 ([1-propyl-11C]8-dicyclopropylmethyl-1,3-dipropylxanthine) was elevated in vivo as a PET ligand for mapping CNS adenosine A1 receptors. METHODS: The regional brain distribution of [11C]KF15372 and the effects of adenosine antagonists on the distribution were determined in mice by tissue sampling. In rats, in which the retinal projection fibres to the superior colliculus had degenerated due to unilateral eye removal, the brain distribution of [11C]KF15372 was visualized by ex vivo autoradiography. RESULTS: The mouse brain uptake of [11C]KF15372 was 1.8% i.d./g at 5 min and then it gradually decreased. The uptake was high in the hippocampus, cerebral cortex, striatum and cerebellum, and was significantly reduced by A1 antagonists but not by A2 antagonists. The brain distribution of 11C assessed by the tissue sampling and autoradiography was compatible with that of the A1 receptors. Autoradiography clearly visualized unilaterally decreased A1 receptor binding in the superior colliculus. CONCLUSION: The results demonstrated that [11C]KF15372 is a selective and high-affinity adenosine A1 receptor ligand and is useful for detecting the degeneration of presynaptic neurons.

Animals↗

PubMed1995

Clinical application of 18F-FUdR in glioma patients--PET study of nucleic acid metabolism.

Positron emission tomography was used to investigate the metabolism of nucleic acids by 18F-fluoro-2'-deoxyuridine (18F-FUdR) in 22 patients with gliomas. Sixteen cases of high grade glioma clearly demonstrated a region of high activity with a differential absorption rate (DAR) of 0.64 +/- 0.34. Six cases of low grade glioma failed to reveal a positive image of the tumor and the DAR in tumor was 0.21 +/- 0.042 (p < 0.01). This PET-18F-FUdR study succeeded in differentiating high and low grade gliomas from the view point of nucleic acid metabolism.

Adult↗

PubMed1995

Synthesis and preliminary evaluation of [1-11C]hexanoate as a PET tracer of fatty acid metabolism.

The potential of [1-11C]hexanoate (11C-HA) as a radiopharmaceutical assessing fatty acid metabolism of the myocardium and brain tissues by PET studies was evaluated. 11C-HA was synthesized by the Grignard reaction of pentylmagnesium bromide and 11CO2. 11C-HA, [1-14C]acetate and [3H]deoxyglucose were simultaneously injected i.v. into mice, and the tissue distribution of the three radionuclides was measured. In the heart, high uptake and rapid clearance of 11C and 14C was found. The brain uptake of 11C was twice as high as that of 14C, and both 11C and 14C decreased slowly compared to the heart. The level of 3H increased with time in both the heart and brain. In fasting conditions, the uptake of 11C by the heart was enhanced and the level of 3H decreased with time. The brain uptake of 11C and 3H was also enhanced. The fasting conditions did not affect the distribution of 14C. The radiation absorbed dose of 11C-HA was also estimated.

Adult↗

PubMed1995

Synthesis of 5-HT3 receptor antagonists, [11C]Y-25130 and [11C]YM060.

Two high-affinity 5-HT3 receptor ligands, Y-25130 and YM 060, have been labeled with 11C for use in PET studies to measure 5-HT3 receptors. The [11C]Y-25130 was prepared by N-methylation of nor-Y-25130-BH3 complex with [11C]CH3I in the presence of K2CO3 followed by HCl hydrolysis. Likewise, N-methylation of nor-YM060 gave [11C]YM060. After HPLC separation, the decay-corrected radiochemical yield of the two 11C-labeled ligands was 34-40% based on [11C]CH3I, the specific activity was 10-12 GBq/mumol at 35-40 min from EOB, and the radiochemical and chemical purities were > 99%. In mice, the brain uptake of the two compounds was the lowest among the tissues investigated, but the level of the brain radioactivity increased with time.

Animals↗

PubMed1995

Synthesis and preliminary evaluation of [11C]KF15372, a selective adenosine A1 antagonist.

As a radioligand for mapping the presynaptic adenosine A1 receptors in the central nervous system by PET, [1-propyl-11C]8-dicyclopropylmethyl-1,3-dipropylxanthine ([11C]KF15372), a selective adenosine A1 antagonist, was prepared by the reaction of 8-dicyclopropylmethyl-3-propylxanthine and [11C]propyl iodide with decay-corrected radiochemical yield of 5% based on the [11C]propyl iodide, radiochemical purity of > 99%, sp. at. of 10-56 GBq/mumol and preparation time of 45-55 min. Another 11C-labeled A1 antagonist with much lower affinity for the A1 receptors, 7-[11C]methyl-KF15372 ([11C]KF17109), was also prepared using [11C]methyl iodide with a decay-corrected radiochemical yield of > 50%. In mice, the brain uptake of [11C]KF15372 (1.91% ID/g at 5 min) decreased gradually with time. Carrier KF15372 competitively reduced the brain uptake to a level (43% of the control) comparable to the brain uptake of [11C]KF17109. On the other hand, an A2 antagonist 3,7-dimethyl-1-propargylxanthine showed no effect on the brain uptake of [11C]KF15372. The results show that [11C]KF15372 has potential as a PET radioligand for mapping the adenosine A1 receptors and that [11C]KF17109 may be a reference compound reflecting the non-specific uptake of the [11C]KF15372.

Animals↗

PubMed1995

Serial positron emission tomography imaging of changes in amino acid metabolism in low grade astrocytoma after radio- and chemotherapy-- Case report.

A 37-year-old male with mixed glioma was treated with combined radio- and chemotherapy. The amino acid metabolism of the tumor site and normal brain was followed by positron emission tomography using [11C]methionine ([11C]Met). The accumulation of [11C]Met in the tumor decreased during therapy and slightly increased 7 months after completion of the therapy, but then decreased markedly. However, computed tomography revealed no notable changes. The contralateral gray matter also showed a gradual decrease of [11C]Met accumulation. These findings indicate that reduction of amino acid metabolism in the tumor continues after radiochemotherapy although neuroimaging reveals no further morphological changes. Such therapy also has long-term effects on normal brain tissue.

Adult↗

PubMed1994

Characterization of [3H]nemonapride binding to mouse brain dopamine D2 receptors assessed in vivo and ex vivo for metabolic modeling in PET studies.

We characterized [3H]nemonapride ([3H]NEM, [3H]YM-09151-2) binding to dopamine D2 receptors. In mice given [3H]NEM with and without sulpiride, the in vivo specific binding of the [3H]NEM to the D2 receptors in the striatum was assessed: SBin vivo-1, striatal uptake minus cerebellar uptake; and SBin vivo-2, uptake in the control mice minus uptake in the sulpiride-treated mice. Tissue homogenates were divided into cytosol and the membrane binding fraction (MB). When the MB was incubated in vitro with sulpiride, the dissociated and nondissociated fractions were defined as the ex vivospecific binding (SBex vivo) and the ex vivo nonspecific binding (NBex vivo), respectively. HPLC revealed that most of the radioactivity in the MB was [3H]NEM, whereas metabolites were found in the cytosol. In the striatum, the SBex vivo increased with time (50% of the total tissue uptake at 60 min), and was equivalent to the SBin vivo-2. The SBin vivo-1 was comparable to the MB. In the cerebral cortex and cerebellum, the SBex vivo decreased with time and the SBex vivo/free [3H]NEM ratios were smaller than those in the striatum.

Animals↗

PubMed1994

Assessment of dopamine metabolism in brain of patients with dementia by means of 18F-fluorodopa and PET.

By means of positron emission tomography (PET) and 18F-fluorodopa (FDOPA), a study was initiated to analyze the cerebral dopamine (DA) metabolism of 32 subjects including those with AD/SDAT and vascular dementia (VD, multi-infarct type). A semiautomated irregular ROI drawing routine to identify the striatum was developed that interactively defined the PET threshold pixels referring to the count histograms and location of the corresponding pixels. A comparative study by five examiners showed significant improvement in the area size definition and count linearity particularly for low contrast objects. The graphical plot was employed to calculate the FDOPA influx rate (Ki) for the ROI data with cerebellar radioactivity as an input function. The striatal Ki value was found to be relatively stable and did not show signs of a significant age-related change. The vascular patients had smaller Ki to the striatum than the aged control. Although the mean Ki of AD/SDAT was almost compatible with that of age-matched normals, their Ki was more scattered with higher and lower Ki cases. The multiple regression analysis revealed that the Ki could be predicted by age and the mini-mental state (MMS) performance (r2 = 0.590, p < 0.01 for AD/SDAT, r2 = 0.401, and p < 0.05 for VD). MMS was found to be a more dominant factor than age. We conclude that dopamine metabolism became disturbed as dementia became progressively severe.

Aged↗

PubMed1994

Multicentric glioma studied with positron emission tomography: a case report.

Positron emission tomography (PET) studies of a multicentric glioma case were undertaken using 11C-methionine (Met) and 18F-fluorodeoxyuridine (FUdR). Met-PET revealed high accumulating lesion in both the left and right hemispheres, whereas in the FUdR-PET, the lesion on the right showed marked accumulation, but not that on the left. For both foci, the histologic diagnoses were anaplastic astrocytoma, but the lesion on the right showed higher density of undifferentiated tumor cells than that on the left. PET studies using Met and FUdR are effective in delineating the proliferative potential of glioma cells, which otherwise cannot be determined by histopathologic studies.

Brain↗

PubMed1994

Synthesis and in vivo evaluation of [11C]semotiadil, a benzothiazine calcium antagonist.

A carbon-11 labeled benzothiazine calcium antagonist, (+)-(R)-2-[5-methoxy-2-[3-[methyl[2-[(3,4- methylenedioxy)phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-2H-1,4- benzothiazin-3(4H)-one (semotiadil), and its enantiomer were prepared by N-methylation of the corresponding norderivatives with 11CH3I: decay-corrected radiochemical yields of 16-27% based on 11CH3I, radiochemical, chemical and optical purity of > 99%, sp. act. of 11-50 GBq/mumol and preparation time of 35-40 min. In mice, saturable and stereo-selective uptake in the hippocampus, striatum and hypothalamus was observed. The potential of the compound to visualize the regional brain calcium channels in vivo by positron emission tomography was indicated; however, no promising sign was found in the myocardium.

Animals↗

PubMed1994

Investigation of tumor invasion with [111In]antimyosin.

Accumulation of [111In]antimyosin in various types of tumors has been reported. In order to test the possibility that the destruction of muscle tissue by tumor invasion could induce high uptake of [111In]antimyosin, we investigated the distribution of [111In]antimyosin in tumor and muscle using autoradiography (ARG). High uptake of [111In]antimyosin was observed both in rabbit papilloma VX2 and rat hepatoma AH109A by scintigraphy and tissue distribution studies, and its concentration was found to be highest at the periphery and outer surface of the tumors using whole-body ARG. However, in micro- and macro-ARG, high grain density was observed in granulation tissue with macrophage infiltration between the tumor and muscle, not in the muscle tissue invaded by tumor cell. Significant non-specific accumulation of [111In]antimyosin in inflammatory tissue surrounding the tumor was suggested.

Animals↗

PubMed1993

Evaluation of the treatment response of lung cancer with positron emission tomography and L-[methyl-11C]methionine: a preliminary study.

We carried out a study to evaluate treatment response and residual mass in lung cancer with positron emission tomography (PET), using L-[methyl-11C]methionine (MET). MET tumour uptake and tumour volume measured by computed tomography (CT) before and within 2 weeks after radiotherapy or chemoradiotherapy were compared in 43 studies of 21 patients. Ten patients with local control (no recurrence) of tumour showed a larger decrease in MET uptake (65.2% +/- 12.2%) than in tumour volume (50.8% +/- 9.6%, P < 0.01). Five patients with early recurrence (from 1 to 4 months) showed smaller decreases in both MET uptake (22.2% +/- 13.5%) and tumour volume (28.6% +/- 20.0%) than those in the no-recurrence group (P < 0.01). Four patients with late recurrence (after 11 months or more) showed a similar decrease to the no-recurrence group in MET uptake (72.8% +/- 14.8%) but little change in tumour volume (18.5% +/- 19.0%), the latter result corresponding to that in the early-recurrence group. Using tumour volume only, the no-recurrence group was differentiated from both the early- and the late-recurrence group (P < 0.01), but the early-recurrence group was not differentiated from the late-recurrence group. Using the MET uptake data, the early-recurrence group was clearly distinguished from the late-recurrence group (P < 0.01), but the late-recurrence group was indistinguishable from the no-recurrence group. CT was useful in distinguishing the no-recurrence group from the groups in which there was ultimate recurrence, whether early or late. When a residual mass is seen on CT, PET seems to be helpful in evaluating tumour viability.

Adenocarcinoma↗

PubMed1993

Immune defense and eosinophilia in congenitally IgE-deficient SJA/9 mice infected with Angiostrongylus costaricensis.

The roles of IgE in protective immunity and eosinophilia in Angiostrongylus costaricensis infection were examined by comparing IgE-deficient SJA/9 mice and IgE-producing SJL/J mice. In primary infection, mean total IgE levels increased to a maximum of 390 ng/ml, which was more than 10 times greater than the 29 ng/ml measured preinfection in SJL/J mice but less than the 10 ng/ml found in SJA/9 mice throughout the experiment. Immune defense as determined by recovery of adult worms and eosinophilia were similar in SJL/J and SJA/9 mice. Protective immunity was induced by infection with A. costaricensis followed by treatment with levamisole for 4-6 days postinfection. After the challenge infection, the numbers of adult worms and eosinophils in SJA/9 mice were not significantly different from those in SJL/J mice. Anti-A. costaricensis IgE antibody was not detected in either strain of mice during the experiment. These results indicate that A. costaricensis infection induced the production of IgE not specific for parasite antigens in IgE-producing mice. Potentiated nonspecific IgE played no significant role in immune defense and eosinophilia.

Angiostrongylus↗

PubMed1993

Brain tumor accumulation and plasma pharmacokinetic parameters of 2'-deoxy-5-18F-fluorouridine.

Using positron emission tomography and radio-high performance liquid chromatography, the accumulation of 2'-deoxy-5-18F-fluorouridine in the brain tumors and plasma pharmacokinetic parameters were investigated in 20 patients. High accumulation of the tracer in high grade gliomas and meningiomas and very rapid degradation of the tracer in the plasma were found. Very large variations were observed in both tumor accumulation and pharmacokinetic data. The tumor accumulation, however, did not correlate with any of the plasma pharmacokinetic parameters: area under the plasma concentration-time curve, mean residence time, total body clearance and steady-state volume of distribution. The results suggest that the accumulation of the tracer reflects the metabolic activity of the brain tumor tissues and that the effect of the rapid metabolic change in the tracer in the plasma on the tumor accumulation may be minor.

Adult↗

PubMed1993

A comparative study on protein incorporation of L-[methyl-3H]methionine, L-[1-14C]leucine and L-2-[18F]fluorotyrosine in tumor bearing mice.

Brain and tumor uptake of L-[methyl-3H]methionine (3H-Met), L-[1-14C]leucine (14C-Leu) and L-2-[18F]fluorotyrosine (18F-Tyr) and their incorporation into the acid-precipitable fraction (APF) were investigated in mice bearing FM3A-P0 and the higher metastatic FM3A-P15A mammary carcinomas in order to compare the potential of positron emitting analogs for measuring protein synthesis rates (PSR) in brain and tumors by positron emission tomography (PET). The total uptake of the 3H-Met by the brain was higher than those of two other amino acids. On the other hand, the incorporation rates into the APF in the brain and tumors were significantly faster with 14C-Leu compared to the others. Most of the 14C in the APF was identified in labeled proteins; however, considerable amounts of 3H were recovered in the lipid and RNA fractions, and 18F was also detected in the lipids. Among the positron emitting analogs of three amino acids, 11C-labeled Leu could be the most suitable for measuring PSR by PET. For all the amino acids, the total uptake and the APF both expressed as the % injected dose seemed slightly higher in the FM3A-P15A than in the FM3A-P0, although the differences did not reach statistical significance.

Animals↗

PubMed1993

Micro-autoradiographic method to study [18F]FDG uptake in mouse tissue.

A new micro-autoradiographic method using 18F (half-life: 109.8 min) was developed to detect 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in mouse tissues. A linear relationship between the number of silver grains and corresponding 18F-radioactivity was observed. The half-distance of spatial resolution with 18F-micro-autoradiography was about 2.1 microns. The grain number increased with exposure time until 6 h, but 7 h or longer exposure induced a characteristic latent image fading. After i.v. injection of [18F]FDG into normal mice, the highest grain level among the hippocampal regions of the brain was found in the stratum lacunosum-moleculare followed by the dentate molecular and the stratum oriens. All granular and pyramidal cell layers showed lower grain levels than neuropil fields. In the pyramidal cell fields, the CA3a contained the highest grain level and the CA4 the lowest. This method requires only 4 h exposure and can be applied to all 18F-tracers to assess the tracer-tissue association.

Animals↗

PubMed1993

Synthesis and characteristics in tumor-bearing mice of N-[11C]methyl-1-deoxynojirimycin and N-[11C]methyl-1-deoxymannojirimycin.

N-[11C]Methyl-1-deoxynojirimycin ([11C]MDNM) and N-[11C]methyl-1-deoxymannojirimycin ([11C]MDMM) were prepared by 11C-methylation of 1-deoxynojirimycin (DNM) and 1-deoxymannojirimycin (DMM), which are specific inhibitors of glucosidase and mannosidase, respectively. In mice bearing Ehrich ascitic tumor, the highest uptake of the [11C]MDNM was observed in the kidney, followed by the liver and small intestine, while the tumor uptake was moderate. By MDNM loading, saturable uptake was observed in these tissues. In homogenates of the kidney and tumor tissues, a considerable amount of radioactivity was detected in a high-molecular weight fraction. These results demonstrate that the [11C]MDNM has a potential for imaging the glucosidase activity by positron emission tomography. On the other hand, [11C]MDMM showed lower uptake than [11C]MDNM in the kidney, liver and small intestine and no effect of carrier DMM, suggesting that the [11C]MDMM would not reflect mannosidase activity.

1-Deoxynojirimycin↗