Biomedical subjects

T Ido

Publications and source records attributed to T Ido.

At least 37 records · Page 2Linked to original sources

PubMed2000

Simplification for measuring input function of FDG PET: investigation of 1-point blood sampling method.

UNLABELLED: The current method for quantitative FDG PET study requires application of multiple arterial blood sampling for measuring the input function, but the procedure is invasive and complicated. The purpose of this study was to establish a 1-point blood sampling technique that gives data comparable with the data of more elaborate serial arterial sampling. METHODS: We established a time point for 1-point arterial sampling that exhibited the highest correlation between plasma radioactivity at the time point and the real integrated value (IV) of the measured input function obtained by multiple arterial sampling in 120 patients and the smallest coefficient of variation of the real IV divided by plasma radioactivity at the time point in 120 patients. Scaling factors for estimation at each sampling point were determined, and a reference table was established to make the supposed input function. RESULTS: The optimal time for 1-point arterial sampling was 12 min after FDG injection. A good correlation was observed between the real IVs and those estimated from 1-point arterial blood sampling at 12 min using the supposed input function (n = 120; P < 0.001). The time point at which the difference between values of arterial and venous blood disappeared was 40 min after FDG injection. The percentage errors of IV estimation by 1-point sampling were 1.70% (n = 120) for arterial blood at 12 min and 3.64% (n = 10) for venous blood at 40 min. CONCLUSION: We conclude that the simplified 1-point sample method works in a manner that is comparable with serial arterial sampling and should be useful for clinical PET.

Adolescent↗

PubMed2000

Visualization of myocardial phosphoinositide turnover with 1-[1-(11)C]-butyryl-2-palmitoyl-rac-glycerol in rats with myocardial infarction.

UNLABELLED: Phosphoinositide turnover mediates the signaling of angiotensin II, which plays a pivotal role in ventricular remodeling after myocardial infarction (MI). We tested the hypothesis that phosphoinositide turnover can be visualized by 1-[1 -(11)C]butyryl-2-palmitoyl-rac-glycerol (11C-DAG) in both infarcted and noninfarcted myocardium after MI in rats. METHODS: Rats received an injection of 11C-DAG 7 d after left coronary artery ligation, and myocardial lipids were extracted from both infarcted and noninfarcted areas of myocardium (n = 3). Metabolites of 11C-DAG were determined by thin-layer chromatography. Quantitative autoradiography of hearts was performed to visualize myocardial phosphoinositide turnover in rats that received an injection of 11C-DAG 1 d (n = 3) and 7 d (n = 5) after MI and 7 d after a sham operation (n = 3). Quantitative autoradiography with 201TlCl was also performed to evaluate myocardial blood flow in rats 7 d after MI (n = 3). Cells occupying the infarcted myocardium were identified by immunohistochemistry. RESULTS: The radioactivity incorporated into the intermediates of phosphoinositide turnover was predominant in both the infarcted (67.1% +/- 5.2% of the total activity) and the noninfarcted (57.4% +/- 3.2%) myocardium. 11C-DAG radioactivity in the infarcted region normalized to that in the noninfarcted region was 1.09 +/- 0.04 in rats 7 d after MI, which was significantly higher than that in rats 1 d after MI (0.38 +/- 0.03, P < 0.001). 201Tl radioactivity in the infarcted region normalized to that in the noninfarcted region was only 0.19 +/- 0.01 7 d after MI. 11C-DAG radioactivity in the noninfarcted region normalized to that in the right ventricular free wall tended to be increased in rats 1 and 7 d after MI compared with the sham-operated rats; the differences, however, were not statistically significant (1.30 +/- 0.15, 1.20 +/- 0.07, and 1.13 +/- 0.02, respectively). Immunohistochemistry revealed that abundant fibroblasts, myofibroblasts, and macrophages occupied the infarcted myocardium 7 d after MI, but the cellularity was low during the first day after MI. CONCLUSION: These data suggest that 11C-DAG may be useful for visualizing regions with activated phosphoinositide turnover after MI. Because wound healing and fibrogenic processes are important factors of ventricular remodeling, 11C-DAG and PET may offer new information benefiting patient management after MI.

Animals↗

PubMed1999

Comparison of the distribution of fluorine-18 fluoromisonidazole, deoxyglucose and methionine in tumour tissue.

To evaluate the tumour imaging potential of fluorine-18 fluoromisonidazole (FMISO), we studied FMISO uptake in an experimental tumour model and examined the correlation between intratumoral distributions of FMISO, 14C-2-deoxyglucose (2DG) and 14C-methionine (Met). The study was performed using control rats with the AH109A tumour and rats with the same tumour under local hypoxia. Tumour uptake of FMISO was constant between 30 min and 2 h after injection, and the tumour to muscle ratio was 2 from 2 to 4 h. A tumour study with FMISO was scheduled at 2 h. Double-tracer autoradiography of the tumour demonstrated that in the areas of high FMISO uptake, there was low uptake of Met, while areas of low FMISO uptake showed high Met uptake. FMISO showed high grain density in the rim of the tumour surrounding the necrotic area. 2DG showed a more uniform distribution over the entire section of viable cells. The mean uptake of FMISO by hypoxic, radioresistant tumours was significantly higher than that by the control tumours (P<0.05), while both 2DG and Met uptake by the control tumours was higher than uptake by hypoxic tumours. When individual tumours were examined, the uptake of FMISO was inversely correlated with that of Met (r = -0.507, P<0.02), while 2DG showed almost uniform uptake with no significant correlation to FMISO. In conclusion, hypoxic and radioresistant tumours could be identified by increased FMISO uptake in our model, consistent with findings reported by others. We found a large overlap in the distribution of FMISO and 2DG within the tumour, but only a small overlap in the distribution of FMISO and Met. A combination of FMISO and other tracers in positron emission tomography or single-photon emission tomography studies might be more helpful than single-tracer studies in predicting the response of tumour tissues to radiotherapy.

Animals↗

PubMed1999

Cloning of cDNA for canine interleukin-18 and canine interleukin-1beta converting enzyme and expression of canine interleukin-18.

Cloning of canine interleukin-18 (IL-18) and canine interleukin-1beta converting enzyme (ICE) cDNA was carried out by using murine IL-18 cDNA and human ICE cDNA, respectively, as probes. Sequence homology to known sequences of human, mouse, or rat genes was noted at nucleotide and amino acid levels. Canine IL-18 mRNA was expressed in various canine organs, whereas canine ICE mRNA was expressed in only a few, particularly in the brain and testis. Cloned canine IL-18 cDNA was expressed in Escherichia coli. The resulting protein promoted induction of canine interferon-y (IFN-y) from stimulated canine lymphocytes. Canine IL-18 and canine IL-12 produced canine IFN-gamma synergistically. Canine IL-18 suppressed the growth of tumor cells transplanted in SCID mice. Cloned canine IL-18 should prove useful as an anticancer agent.

Amino Acid Sequence↗

PubMed1999

FDG PET evaluation of residual masses and regrowth of abdominal lymph node metastases from colon cancer compared with CT during chemotherapy.

Fluorine-18-2-deoxy-2-fluoro-D-glucose (F-18 FDG) PET may be more suitable for follow-up after cancer treatment than other morphologic approaches, because it reflects tumor viability. A patient with abdominal lymph node metastases from colon cancer was followed by CT and F-18 FDG PET during chemotherapy. F-18 FDG PET tumor images changed in accordance with the clinical progress, whereas CT findings were relatively unchanged. This case clearly shows the utility of F-18 FDG PET for follow-up during cancer chemotherapy.

Abdominal Neoplasms↗

PubMed1999

18F-FDG PET imaging of muscle activity in runners.

UNLABELLED: PET with three-dimensional data acquisition using 18F-fluorodeoxyglucose (FDG) was applied to evaluate skeletal muscle activity in runners. METHODS: Seven healthy adult male volunteers were studied. They ran for a total of 35 min, 15 min before and 20 min after intravenous injection of FDG. Another 7 adult male control subjects were also examined at rest. Images obtained through a set of whole-body PET scans were analyzed. Regions of interest (ROIs) were manually drawn on images of muscles of both thighs, legs and feet, and the standardized uptake ratio (SUR) and total radioactivity distribution (TRD) for each region were calculated. RESULTS: The work load was below the anaerobic threshold. SUR of foot, leg and thigh were low at rest but during running increased 5.19, 4.30 and 1.74 times, respectively. The SUR of posterior-to- anterior compartment of the leg was 1.1+/-0.1 at rest and 1.6+/-0.5 (P < 0.01) during running. The laterality index of both SUR and TRD changed significantly only in the foot of the dominant side during running. TRD of the leg, less than half that of the thigh at rest, became equivalent to that of the thigh during running. TRD of the foot did not change significantly. CONCLUSION: Sole muscles showed highest metabolic activation per unit volume during running, which was higher in the dominant side. Comparison of whole muscle activity during running indicated the highest metabolic activation was in the posterior compartment of the leg, whereas thigh muscles showed relatively little changes during running. Our data indicate that whole-body FDG PET, especially three-dimensional data acquisition, is a useful tool for the investigation of muscular activity during exercise.

Adult↗

PubMed1998

Sensitization of cells to ionizing radiation by chlorin e6Na.

We have investigated whether a hydrophilic photosensitizer, chlorin e6Na (Ce6Na), can sensitize cells to ionizing radiation. When V79-1 cells were pretreated with Ce6Na for 2 hr before receiving a dose of 2-14 Gy of irradiation, the cells became sensitive to X-irradiation. The sensitizing effect of Ce6Na depended on the dose of Ce6Na. The sensitizing effect also depended on the length of the treatment period before X-irradiation up to 4 hr, but not on the length of a treatment period after X-irradiation. Intracellular concentrations of Ce6Na were increased linearly after incubation with Ce6Na for periods of up to 4 h. The dose-modifying factor calculated from the survival curve was 1.25.

Animals↗

PubMed1998

Development of a new method for simultaneously evaluating mucociliary clearance and pulmonary epithelial permeability in rabbit experiments by means of 18FDG, three-dimensional positron emission tomography and rectilinear scan.

We tried to simultaneously obtain the elimination constant of mucociliary clearance and the pulmonary epithelial permeability constant after inhalation of 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) solution by carrying out whole lung positron emission tomography and a rectilinear scan in rabbit experiments. The elimination constant of pulmonary epithelial permeability was obtained from the decrease in the amount of the radioactivity with time in the region of interest (ROI) confined to the lungs, trachea and tracheal cannula in the rectilinear scan. The total elimination constant of the radioactivity in the lungs was obtained from the ROI confined to the lungs in the tomography. The mucociliary clearance rate constant in the lungs was then obtained after subtracting the elimination constant of the pulmonary epithelial permeability from the total elimination constant of the 18FDG in the lungs. The mucociliary clearance constant in the trachea was calculated from the residual radioactivity in the trachea and the mucociliary clearance constant in the lungs. The mean pulmonary epithelial permeability constant was 0.0020% min(-1) obtained from the rectilinear scan. The mean mucociliary clearance constants of the lungs and the trachea were 0.0006 and 0.025% min(-1), respectively. These results indicated that the pulmonary epithelial permeability and mucociliary clearance could be evaluated simultaneously with 18FDG by using three-dimensional positron emission tomography and a rectilinear scan.

Administration, Inhalation↗

PubMed1998

Heterogeneous fatty acid uptake early after reperfusion in rat hearts.

We determined whether spatial distributions of substrate uptake are heterogeneous within the area at risk during reperfusion. Quantitative autoradiography with imaging plates and two long-lived radioisotopes was applied to 15 open-chest, anesthetized rats subjected to 30 min of coronary artery ligation and 30 min of reperfusion. Regions showing increased beta-methyl-[1-14C]heptadecanoic acid ([14C]BMHDA) uptake (166 +/- 17% of that in the nonischemic area) appeared at the lateral borders and subepicardial layer within the area at risk, and 2-deoxy-D-[1-3H]glucose ([3H]DG) uptake was 103 +/- 24% in these regions. Regions with decreased [14C]BMHDA uptake (28 +/- 11%) occupied the midmyocardial layer except at the lateral borders within the area at risk, and [3H]DG uptake was 62 +/- 18% in these regions. The percentage interregional coefficients of variation (index of heterogeneity) in [14C]BMHDA uptake, [3H]DG uptake, and blood flow were higher in the area at risk than in the nonischemic area (76 +/- 23 vs. 21 +/- 7%, 39 +/- 10 vs. 21 +/- 7%, and 49 +/- 19 vs. 14 +/- 4%, respectively). Heterogeneous distributions of substrate uptake may explain the conflicting results concerning substrate metabolism during reperfusion.

Animals↗

PubMed1998

Deposition and clearance of inhaled 18FDG powder in patients with chronic obstructive pulmonary disease.

As freon is limited in its use as a generator for aerosol inhalation, powder particles are used as an alternative for inhalation therapy. The pulmonary deposition and clearance of inhaled powder particles was studied by positron emission tomography (PET) in ten patients with chronic obstructive pulmonary disease (COPD) and in five normal controls. The powder, 5 microm in mean diameter, was water soluble and labelled with 2-deoxy-2-[18F]-fluoro-D-glucose (18FDG). Powder inhalation was done with single deep inspiration from residual volume to total lung capacity. The initial deposition ratio in the right or left lung field to total inhaled dose, measured by an anteroposterior rectilinear scan, did not differ between normals and COPD patients. Ratios of radioactivity detected within the central and peripheral regions (the central to peripheral ratio) measured by the PET scan was not significantly different between COPD patients (4.8+/-2.6, mean+/-SD) and normals (2.6+/-0.8, mean+/-SD). However, the regional powder deposition in peripheral lung fields measured by the PET scan was significantly more uneven in COPD patients than in normal patients. The clearance rate of 18FDG, defined as the retention ratio of 18FDG activity to the initially deposited 18FDG at 60 and 120 min after inhalation, in the trachea, large bronchi or peripheral lung fields measured by tomographic scan showed a wider variation in COPD patients than in normals. To conclude, inhaled powder tended to be deposited more centrally and was distributed more unevenly in the peripheral lung in chronic obstructive pulmonary disease patients than in normals. This could be a limitation of powder inhalation used for therapy in chronic obstructive pulmonary disease patients.

Administration, Inhalation↗

PubMed1998

Biodistribution study of murine monoclonal anti-GD3 antibody in nude mice bearing human melanoma xenografts for development of immunoscintigraphy.

Reactivity of the monoclonal antibody with the tumor markers is known to be different between cultured cells in vitro and transplanted tumors in vivo. The monoclonal antibody should be investigated regarding its specific accumulation in tumor-bearing mice for immunodetection or immunotherapy. We studied the biodistribution of radiolabeled monoclonal anti-GD3 antibody (IgM) in normal mice and nude mice bearing human melanoma xenografts. Tissue-to-blood distribution ratios of the antibody in the liver, spleen and kidney increased with time in both normal and melanoma-transplanted mice, but no significant changes were observed in other normal tissues up to 5 days after injection. Specific accumulation of the monoclonal anti-GD3 antibody in the grafted human melanoma (HMV-II) was observed 4 and 5 days after injection. On the other hand, no specific accumulation of standard murine IgM in the tissue of HMV-II was observed in mice bearing the HMV-II xenograft 5 days after injection. Because the tissue-to-blood ratio of the distribution in the tissue of HMV-II became larger than that of other tissues 4 and 5 days after administration, 4 days after the administration of the monoclonal anti-GD3 antibody were required for immunoscintigraphy. Accumulation of the monoclonal anti-GD3 antibody in other human melanomas (HMV-I, HMY-1 and SK-MEL188) inoculated into mice was also observed 4 days after the antibody administration. The monoclonal anti-GD3 antibody used in this study would be useful in immunodetection or immunotherapy.

Animals↗

PubMed1998

Fluorine-18-labeled fluoroboronophenylalanine PET in patients with glioma.

UNLABELLED: We synthesized fluorine-18-labeled fluoroboronophenylalanine (18F-10B-FBPA), an analog of boronophenylalanine (10B-BPA), and characterized its pharmacokinetics in patients with glioma. We conducted PET studies on three types of gliomas to clarify the relationship between tumor grade and each rate constant [K1 (ml/g/min), k2 (min[-1]) and k3 (min[-1])], and here, we discuss the metabolism of the 10B-BPA analog (18F-10B-FBPA). METHODS: Thirty-three cases of primary gliomas were studied by dynamic PET using DL-18F-10B-FBPA or L-18F-10B-FBPA. Dynamic PET images of 18F-10B-FBPA incorporation into tumors were obtained, and the arterial blood samplings were performed in all cases. RESULTS: When the dynamic PET data were represented as Gjedde-Patlak plots, there was a positive slope, suggesting the involvement of the putative metabolic pool of this tracer. A three-compartment model using rate constants (K1, k2 and k3) was used for the kinetic analysis. The accumulation of 18F-10B-FBPA was found to correlate with the degree of malignancy, and the L form of 18F-10B-FBPA was taken up better than was the DL form. The results of dynamic PET analysis suggested that K1 (measuring amino acid transport process) is a major factor determining the accumulation of 18F-10B-FBPA. A comparison of the rate constants revealed that k3 (metabolic process) did not correlate with the degree of malignancy. The absence of evident differences in k3 between DL and L forms suggests that k3 represents phenomena that are not dependent on the native form of L. CONCLUSION: These PET data will be of practical use for diagnosis of malignancy and direct prediction of the effectiveness of boron neutron capture therapy using 10B-BPA.

Astrocytoma↗

PubMed1998

Positron emission tomography-based boron neutron capture therapy using boronophenylalanine for high-grade gliomas: part I.

Determination of tumor boron-10 (10B) levels is required for accurate neutron dosimetry during boron neutron capture therapy. We assessed a new method for quantitative measurement of boronated drug uptake in high-grade gliomas. This method uses positron emission tomography (PET) with fluorine-18-labeled L-fluoroborono-phenylalanine (L-18F-10B-FBPA), which was synthesized as an analogue of L-boronophenylalanine. We studied the accumulation of L-18F-10B-FBPA by PET in patients with high-grade gliomas. Dynamic PET studies of brain tumors revealed that L-18F-10B-FBPA accumulated gradually after bolus injection, and the value of PET activity divided by the integrated plasma activity reached a constant level 42 min after injection, which was defined as the incorporation constant (Ic*). This constant reflected the appropriate L-18F-10B-FBPA accumulation in tumor tissue. Based on the Ic* constant, the methods for estimating tumor 10B concentration were devised. With this method, the estimated values of 10B concentration in gliomas were very close to the 10B levels in surgical specimens. This method was based solely on PET and can potentially provide data that would assist in the selection of patients for future treatment with boron neutron capture therapy after surgical resection of their brain tumors.

Boron↗

PubMed1998

Positron emission tomography-based boron neutron capture therapy using boronophenylalanine for high-grade gliomas: part II.

Based on pharmacokinetic findings of fluorine-18-labeled L-fluoroboronophenylalanine by positron emission tomography (PET), methods for estimating tumor 10B concentration were devised. In clinical practice of boron neutron capture therapy (BNCT) for high-grade gliomas, a large amount of L-boronophenylalanine (L-10B-BPA)-fructose solution is used. Under these conditions, a slow i.v. infusion of L-10B-BPA-fructose solution should be performed for BNCT; therefore, the changes over time in 10B concentration in the target tissue were estimated by convoluting the actual time course of changes in plasma 10B concentration with a PET-based weight function including the proper rate constants [K1 (ml/g/min), k2 (min(-1)), k3 (min(-1)), and k4 (min(-1))]. With this method, the estimated values of 10B concentration in gliomas were very close to the 10B levels in surgical specimens. This demonstrated the similarity in pharmacokinetics between fluorine-18-labeled L-fluoroboronophenylalanine and L-10B-BPA. This method, using the appropriate rate constant, permits the determination of tumor 10B concentration and is widely suitable for clinical BNCT, because the averaged PET data are enough to use in future patients without individual PET study.

Boron↗

PubMed1997

Effects of haloperidol and cocaine pretreatments on brain distribution and kinetics of [11C]methamphetamine in methamphetamine sensitized dog: application of PET to drug pharmacokinetic study.

Repeated administration of methamphetamine (MAP) causes behavioral sensitization in animals. We previously reported that the maximum accumulation level of [11C]MAP in the MAP-sensitized dog brain was 1.4 times higher than that in the control. In behavioral studies, haloperidol (a dopamine D2 receptor antagonist) prevents MAP-induced behavioral sensitization, and cocaine (a dopamine reuptake blocker) has the cross-behavioral sensitization with MAP. In the present study, to elucidate the relation between the MAP-induced behavioral sensitization and the pharmacokinetics of MAP, we investigated the effects of haloperidol and cocaine pretreatments on brain regional distribution and kinetics of [11C]MAP using positron emission tomography (PET). A significant increase of [11C]MAP uptake into the sensitized dog brain was prevented by haloperidol and cocaine pretreatments. These pharmacokinetic changes were not due to the changes in the rate of MAP metabolism. These results suggest haloperidol and cocaine can change the cerebral pharmacokinetic profile of MAP in the behavioral-sensitized dog. The variations of MAP-accumulation may affect the development or expression of MAP-induced behavioral sensitization.

Animals↗

PubMed1997

In vivo diagnosis of human malignant melanoma with positron emission tomography using specific melanoma-seeking 18F-DOPA analogue.

Detection and diagnosis of human malignant melanoma by Positron Emission Tomography (PET) using 18F-10B-L-BPA, a specific melanogenesis-seeking compound synthesized for use in Boron Neutron Capture Therapy for malignant melanoma (NCT), has been developed. This resulted in a novel, highly effective methodology for the selective three dimensional imaging of metastatic malignant melanomas, and for accurate determination of 10B concentration in the tumor and surrounding tissue, providing almost all diagnostic information necessary for complete non-invasive radiation dose planning in the treatment of malignant melanoma both for NCT as well as other therapeutic modalities.

Boron↗

PubMed1997

Heterogeneity of myocardial fluoro-18 2-deoxyglucose uptake in patients with apical hypertrophic cardiomyopathy.

We have shown that myocardial glucose metabolism is heterogeneous in patients with hypertrophic cardiomyopathy. It is not known, however, whether glucose metabolism is impaired in patients with apical hypertrophic cardiomyopathy, which is fairly common in Japan. We studied 7 patients with apical hypertrophic cardiomyopathy and 5 normal subjects using fluoro-18 2-deoxyglucose (FDG) and positron emission tomography (PET). We calculated regional FDG fractional uptake and the inter-regional coefficient of variation (CV) of FDG fractional uptake in the interventricular septal, anteroapical, and posterolateral regions. The regional FDG fractional uptake was similar in the 2 groups and among the 3 different segments within each group. However, the inter-regional CV of FDG fractional uptake was increased in the anteroapical wall segment of the patient group compared with the control group and also with the other 2 regions in the patient group. The results did not differ when we studied another 5 patients and 6 normal control subjects with a PET scanner with higher spatial resolution. These data suggest that myocardial glucose metabolism may be impaired in the anteroapical wall segment of patients with apical hypertrophic cardiomyopathy.

Adult↗

PubMed1997

Myocardial glucose metabolism is different between hypertrophic cardiomyopathy and hypertensive heart disease associated with asymmetrical septal hypertrophy.

Myocardial glucose metabolism has been shown to be heterogeneous in patients with hypertrophic cardiomyopathy (HCM). We tested the hypothesis that myocardial glucose metabolism differs between patients with HCM and those with hypertensive heart disease (HHD) associated with asymmetrical septal hypertrophy. We studied 12 patients with HCM, 7 HHD patients associated with asymmetrical septal hypertrophy using 18F 2-deoxyglucose (FDG) and positron emission tomography. We calculated % FDG fractional uptake in the inter-ventricular septum and posterolateral wall. Heterogeneity of FDG uptake was evaluated by % interregional coefficient of variation of FDG fractional uptake in each wall segment. In both the interventricular septum and posterolateral wall, % FDG fractional uptake was not significantly different between the two groups. The % interregional coefficient of variation for both interventricular septum (10.6 +/- 1.6 vs. 4.1 +/- 0.5, p < 0.01) and posterolateral wall (5.9 +/- 0.7 vs. 3.8 +/- 0.5, p < 0.05) was significantly larger in patients with HCM than in HHD patients associated with asymmetrical septal hypertrophy. Echocardiography demonstrated that the degree of asymmetrical septal hypertrophy was similar between the two groups. These results suggest that myocardial glucose metabolism may be more heterogeneous in patients with HCM compared to HHD patients associated with asymmetrical septal hypertrophy, although the left ventricular shape is similar. The difference in the heterogeneity might have resulted from differences in the pathogeneses of the two diseases.

Adolescent↗