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Biomedical subjects

T Ido

Publications and source records attributed to T Ido.

At least 91 records · Page 5Linked to original sources
PubMed1994

[Carbon-11 labeled diacylglycerol for signal transduction imaging: effect of the solubilizer on the distribution and radiation dosimetry].

Carbon-11 labeled diacylglycerol (11C-DAG) has been developed as a signal transduction imaging agent for the CNS, and it can visualize the second messenger. For clinical application by positron CT (PET), the 11C-DAG solution must be prepared for intravenous injection. However, the 11C-DAG does not dissolve in water because of its lipophilicity and requires a solubilizer such as human serum albumin (HSA) and Tween 80 (TW-80). We examined the influence of these solubilizers on the tissue distribution of 11C-DAG, and estimated the radiation dosimetry. In the brain, uptake of 11C-DAG dissolved with HSA was 1.3-1.8 times higher than that of dissolved with TW-80. On the other hand, the lung and spleen showed a higher uptake of 11C-DAG using TW-80 than when using HSA. Especially, the lungs showed 20-40 times higher uptake than when using HSA. Also, the washout of radioactivity from tissue was slower, and the dose of radiation exposure was estimated to be higher, with TW-80 than with HSA. Therefore, between TW-80 and HSA with different solubilizing mechanisms, the later was suggested to be a better solubilizer of 11C-DAG.

Animals↗
PubMed1994

Active and passive mechanisms of [fluorine-18] fluorodeoxyglucose uptake by proliferating and prenecrotic cancer cells in vivo: a microautoradiographic study.

UNLABELLED: In this study, [18F]FDG uptake mechanisms were investigated in neoplastic cells during cell proliferation and cell death. METHODS: Detailed analysis was performed on mouse tumor models of different growth rates using [18F]FDG, [6-13H]thymidine [3H]Thd (a precursor of DNA synthesis) and [125I]bovine serum albumin ([125I]BSA) (a marker of diffusion) with autoradiographic and histopathologic techniques and electron microscopy. RESULTS: The three compounds, [18F]FDG, [3H]Thd and [125I]BSA, showed different heterogeneous patterns of distribution within tumor tissue sections in neoplastic and non-neoplastic cellular elements. The uptake of [18F]FDG by prenecrotic (or necrobiotic) tumor cells surrounding focal necrotic cell debris was 1.5 to 2.3 times higher than that of viable tumor cells. Prenecrotic cells did not retain trapped [18F]FDG; therefore, the uptake was considered to be nonmetabolic. Inconspicuous cell membrane, vesicular cytoplasmic organelles and condensed nuclear chromatin were remarkable findings in the prenecrotic cells. A comparison of viable tumor cells in tumors undergoing different growth rates showed that the ratio of [18F]FDG uptake was similar to that of [3H]Thd uptake in each S-phase cell. Fluorine-18-FDG showed a cell cycle dependency, with a higher uptake observed in cells in G0/G1 and G2 phases of the cell cycle compared with the S and M phases. CONCLUSION: A passive mechanism of [18F]FDG uptake may exist in the necrobiotic/prenecrotic or hypoxic/anoxic cells in tumors. However, the discordance of [18F]FDG and [3H]Thd uptake may be the result of the different cell cycle dependency of tracer uptake in the same tumor.

Animals↗
PubMed1994

Microautoradiographic study for the differentiation of intratumoral macrophages, granulation tissues and cancer cells by the dynamics of fluorine-18-fluorodeoxyglucose uptake.

UNLABELLED: A substantial amount of macrophage infiltration occurs in both human and animal tumors. We previously showed that 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake was higher in tumor-associated macrophages and young granulation tissues than in tumor cells. Differentiation of intratumoral non-neoplastic cells from neoplastic cells is important not only for the reduction of false-positives in FDG-PET tumor studies but also for patient management. METHODS: A time-course study was performed using micro- and macro-autoradiography and tissue distribution in C3H/He mice bearing transplanted syngeneic FM3A mammary carcinoma and MH134 hepatoma was evaluated to analyze the intratumoral cellular dynamics of [18F]FDG and 2-deoxy-D-[3H]glucose in vivo. RESULTS: The volume-doubling time in vivo was 1.3 days for MH134 and 4.9 days for FM3A, and the survival time of the host was 32.1 and 40.3 days, respectively. The peak uptake of both tracers in the tumor was 60 min after intravenous injection. The uptake by MH134 was 1.7-2.1 times higher than that by FM3A. The intracellular concentration as determined by counting the silver grains on micro-autoradiographic sections showed that the uptake by macrophages and focal small necrotic areas in both tumors was faster than the blood clearance until 15 min after tracer injection. CONCLUSION: Thus, non-neoplastic cellular elements can be differentiated from viable neoplastic cells by means of the dynamic analysis of [18F]FDG uptake.

Animals↗
PubMed1994

Accumulation of 2-deoxy-2[18F]fluoro-D-glucose in human cancers heterotransplanted in nude mice: comparison between histology and glycolytic status.

UNLABELLED: The success of tumor imaging with PET and 2-deoxy-2-fluoro[18F]-D-glucose (18FDG) is based on preferential accumulation of 18FDG in tumors. METHODS: Fluorine-18-FDG uptake was measured in nine human cancers heterotransplanted in nude mice and compared with histologic subclassification. RESULTS: Mean 18FDG uptake by the human cancers was considerably less than that by the host's heart, but values at 60 min after injection were about 2.5 times as high as the liver and kidney, about two times as that for the muscle and about six times that for the blood. Comparison of 18FDG uptake and histological grade in four gastric, two pancreatic and three colonic cancers showed that 18FDG uptake increased with loss of differentiation. CONCLUSION: This nude mice model system is useful for studying correlations between physiological and morphological parameters of heterotransplanted human cancers.

Animals↗
PubMed1993

Liposome targeting to rat brain: effect of osmotic opening of the blood-brain barrier.

To determine whether sulfatide liposomes can cross the blood-brain barrier (BBB) with or without osmotic treatment by mannitol, we administered liposomes through the internal carotid artery in rats. Sulfatide liposomes could pass the BBB with osmotic treatment, but not without osmotic treatment. Therefore, we propose that the combination method of administration of the reticuloendothelial-system avoiding liposomes with osmotic treatment can be useful for treatment of various kinds of brain diseases.

1,2-Dipalmitoylphosphatidylcholine↗
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

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

6-[18F]fluorodopa metabolism in patients with hemiparkinsonism studied by positron emission tomography.

A group of 10 healthy control subjects and 10 patients with hemiparkinsonism (HD) were studied by positron emission tomography (PET) using 6-[18F]fluorodopa (FDOPA). FDOPA metabolism in the caudate nucleus and the putamen was separately estimated by measuring target-to-background ratios (TBRs) using composite images added between 30 and 60 min after FDOPA injection and by TBR-versus-time slopes during PET study. TBRs in the caudate nucleus and the putamen were 1.81 +/- 0.23 (mean +/- SD) and 1.92 +/- 0.28 in the 10 controls, respectively. In HD patients, on the dominantly affected hemisphere related to main clinical symptoms, TBRs were significantly decreased in the caudate nucleus (P < 0.01) and the putamen (P < 0.05) compared with those in the corresponding areas on the contralateral hemisphere, though those TBRs on both hemispheres were significantly decreased compared with the TBRs of normal subjects (P < 0.01). TBRs and TBR slopes in both the caudate nucleus and the putamen were correlated with disease severity according to Hoehn and Yahr. On the dominantly affected hemisphere, TBR and TBR slopes in the putamen were well correlated with individual clinical measures for bradykinesia and rigidity, and those in the caudate nucleus were also correlated with the severity of tremor. Our data suggest that in HD patients, PET study using FDOPA may provide unique and efficient information on the dysfunction of the dominantly affected caudate nucleus and the putamen which are correlated with diseased severity and individual clinical symptoms.

Adult↗
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

Cellular accumulation of 18F-labelled boronophenylalanine depending on DNA synthesis and melanin incorporation: a double-tracer microautoradiographic study of B16 melanomas in vivo.

The cellular distribution of 4-borono-2-[18F]fluoro-L-phenylalanine ([18F]FBPA, an analog of p-boronophenylaline), a potential agent for boron neutron capture therapy (BNCT), and [6-3H]thymidine ([3H]Thd, a DNA precursor) in murine two B16 melanoma sublines and FM3A mammary carcinoma was studied in vivo using double-tracer microautoradiography. Tumour volume, tumour age, cell density in the tissues and the proportion of S phase cells in the cell cycle were the same in the three tumour models. Volume doubling time, which represents tumour growth rate, was fastest in B16F10, followed by B16F1 (P < 0.05), the slowest being in FM3A (P < 0.001). The rate of DNA synthesis in S phase cells corresponded to the volume doubling time. The greatest amount of [18F]FBPA was observed in S phase melanocytes and the lowest amount was found in non-S phase non-melanocytes. The [18F]FBPA accumulation was primarily related to the activity of DNA synthesis and, secondarily, to the degree of pigmentation in melanocytes. The therapeutic efficacy of BNCT with p-boronophenylalanine may be greater in melanoma that exhibits greater DNA synthesis activity and higher melanin content.

Animals↗
PubMed1993

Simultaneous demonstration of neurotransmitter and receptor systems of the rat brain using in vivo double autoradiography.

Neurotransmitter and receptor systems of the rat brain were simultaneously observed by in vivo double autoradiography using a novel imaging plate analyzer system which was developed by Fuji Photo Film Co., Ltd. The animals were subjected to intravenous administration of [18F]-6-fluoro-L-dopa ([18F]-DOPA) and [3H]YM-09151-2, a highly selective dopamine D2 antagonist. The radioactivities of [18F]-DOPA and [3H]YM-09151-2 were found to be highly concentrated in the striatum, demonstrating presynaptic and postsynaptic sites of the dopaminergic nigrostriatal tract, respectively. The [3H]YM-09151-2 was also found to be accumulated in the substantia nigra which is known to correspond with the distribution of dopamine D2 receptors. This method was shown to be useful for investigation of animal models with brain diseases.

Animals↗
PubMed1993

Protein kinase C imaging using carbon-11-labeled phorbol esters: 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate as the potential ligand for positron emission tomography.

Protein kinase C plays a crucial role in signal transduction for a variety of biologically active substances which activates cellular functions and their proliferation. The actions are closely related to both normal and abnormal functions in the nervous system. Tumor-promoting phorbol esters can substitute for diacylglycerols which are important ligands that bind to protein kinase C. Three typical phorbol esters, phorbol 13-[1-11C]butyrate, phorbol 12,13-[1-11C]dibutyrate and 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate, were synthesized by using [11C]ethylketene with a high specific activity (186GBq/mumol). Their in vivo autoradiograms demonstrated a heterogenous distribution in rat brain. 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate was particularly suited for in vivo use due to its nontumor-promoting activity and its ready permeability to the blood-brain barrier. High optical density was observed in the cortex, amygdala and hippocampus. The in vivo binding properties of this compound to protein kinase C were confirmed by in vivo displacement studies with unlabeled 12-deoxyphorbol 13-isobutyrate-20-butyrate and unlabeled phorbol 12,13-dibutyrate. This suggests that 12-deoxyphorbol 13-isobutyrate-20-[1-11C] butyrate has a specific binding affinity for protein kinase C.

Animals↗
PubMed1992

Histamine H1 receptors in human brain visualized in vivo by [11C]doxepin and positron emission tomography.

Histamine H1 receptors in the living human brain were visualized by positron emission tomography (PET) using [N-11C-methyl]-(E)-doxepin ([11C]doxepin). The regional distribution of the carbon-11-labeled compound in the brain corresponded well with that of the histamine H1 receptors measured in vitro using [3H]pyrilamine. The radioactivity in the brain was significantly reduced by intravenous pretreatment with d-chlorpheniramine (5 mg), a histamine H1 antagonist. The regional distribution of [11C]doxepin in the brain 45-90 min after its injection was almost the same as that of [11C]pyrilamine in the brain. These results indicate that [11C]doxepin is useful for measuring histamine H1 receptors in human brain by PET.

Adult↗
PubMed1992

Differences in myocardial fluoro-18 2-deoxyglucose uptake in young versus older patients with hypertrophic cardiomyopathy.

The purpose of this study was to determine whether regional myocardial glucose use in patients diagnosed as having hypertrophic cardiomyopathy (HC) at a younger age differs from that in those diagnosed at middle to old age. Sixteen patients with HC (group 1 aged less than 40 years (n = 8); group 2 aged greater than 40 (n = 8) were studied using positron emission tomography and fluoro-18 2-deoxyglucose (FDG). All patients were diagnosed as having HC within 6 years of the study. Contiguous regions of interest were selected circumferentially on each cross-sectional image of the left ventricular wall. In each region of interest, % FDG fractional uptake was calculated. In each patient, % left ventricular FDG fractional uptake was determined as a mean value of % FDG fractional uptake in each region of interest. Moreover, as a measure of nonhomogeneity, the % interregional coefficient of variation in FDG fractional uptake was calculated in each patient. Whereas % left ventricular FDG fractional uptake did not differ between the 2 groups, the % interregional coefficient of variation in FDG fractional uptake was increased in group 1 compared with that in group 2 (11.5 +/- 3.6 vs 7.4 +/- 1.6%; p less than 0.02). Interventricular septum/left ventricular posterior wall thickness ratio and total counts in cross-sectional image did not differ between the 2 groups. These data suggest that patients diagnosed as having HC at a younger age have more nonhomogeneous myocardial metabolic characteristics than do patients diagnosed at middle or old age, and support the notion that HC in the young may be different from that in the middle-aged or elderly.

Adolescent↗
PubMed1992

On-line [11C]methylation using [11C]methyl iodide for the automated preparation of 11C-radiopharmaceuticals.

A novel method for the efficient preparation of 11C-radiopharmaceuticals by on-line [11C]methylation using [11C]methyl iodide has been developed and applied to a rapid, convenient automated system. [11C]Methyl iodide is first trapped in a short column, containing an adsorber and coated substrate, which is connected to an HPLC injector. DMF is then introduced. Alternatively the substrate is added with the DMF. A whole reaction mixture can be easily injected onto an HPLC column for purification by switching the injector valve immediately after the reaction. Thus, radiochemical yields in the preparation of 11C-labeled doxepin, benztropine, cyproheptadine and N-methylspiperone have been improved remarkably and the synthetic procedure simplified.

Benztropine↗