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Biomedical subjects

Y Fujibayashi

Publications and source records attributed to Y Fujibayashi.

At least 91 records · Page 5Linked to original sources

Myocardial accumulation of iodinated beta-methyl-branched fatty acid analog, [125I](p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP), and correlation to ATP concentration--II. Studies in salt-induced hypertensive rats.

This study investigates the possible relationship between myocardial [125I]BMIPP accumulation and ATP concentration, in the salt-induced hypertensive Dahl-strain rats. [125I]BMIPP accumulation in the myocardium was inversely related to the degree of hypertension. On the other hand, ATP levels increased in the myocardium of rats with higher blood pressure showing an inverse relationship with BMIPP accumulation. Further studies are required for elucidating these possible inter-related phenomena.

Adenosine Triphosphate↗

A new approach to the integrity of dual blood-brain barrier functions of global ischemic rats. Barrier and carrier functions.

BACKGROUND AND PURPOSE: We studied the influence of reperfusion on carrier and barrier functions of the blood-brain barrier after transient global ischemia in rats. METHODS: We used iodine-125-labeled 3-iodo-alpha-methyl-L-tyrosine and carbon-14-labeled sucrose as tracers for studying carrier and barrier functions of the blood-brain barrier, respectively. Brain uptakes of these two tracers were measured in Wistar rats subjected to either 15- or 30-minute four-vessel occlusion developed by Pulsinelli and Brierly before recirculation for 3, 6, 24, 48, and 72 hours. Tracer (5 microCi) was injected intravenously in each rat 30 minutes before killing the animal. RESULTS: Following 15- or 30-minute ischemia, [14C]sucrose uptakes were significantly higher at 3 and 6 hours of reperfusion before recovery to control values after reperfusing for 24 to 48 hours in almost all brain regions. However, a rebound in radioligand uptake was significantly manifested in some sites at 72 hours after reperfusion (p < 0.05 to p < 0.01). Uptakes of 125I-3-iodo-alpha-methyl-L-tyrosine were brain site-dependent: significantly (p < 0.05) higher in cortex (3 and 48 hours after reperfusion) and thalamus (3, 6, and 48 hours after reperfusion) but significantly (p < 0.05 to p < 0.01) lower in striatum, cortex (72 hours after reperfusion), and midbrain (6, 24, and 72 hours after reperfusion). Because the [14C]sucrose uptake in brain was 10% lower than that of 125I-3-iodo-alpha-methyl-L-tyrosine, the change in absolute transport of the latter tracer was approximated to its brain uptake. CONCLUSIONS: The carrier and barrier functions of the blood-brain barrier should be evaluated separately. The radioligand 125I-3-iodo-alpha-methyl-L-tyrosine may serve as a useful tool to evaluate the carrier function of the blood-brain barrier after transient cerebral ischemia in rats.

Animals↗

Mitochondria-selective reduction of 62Cu-pyruvaldehyde bis(N4-methylthiosemicarbazone) (62Cu-PTSM) in the murine brain; a novel radiopharmaceutical for brain positron emission tomography (PET) imaging.

The retention mechanism of 62Cu-pyruvaldehyde bis(N4-methylthiosemicarbazone) (62Cu-PTSM) in the murine brain was evaluated. For this purpose, stable Cu-PTSM was subjected to electron spin resonance spectrometry (ESR) and high performance liquid chromatography (HPLC) analysis to determine the valence state, coordination structure and tissue metabolism. In murine brain homogenate, ESR and HPLC analysis indicated the reduction and cleavage of Cu(II)-PTSM to Cu(I). This virtually irreversible reduction was specifically initiated by the mitochondrial enzymatic system in the murine brain.

Animals↗

Studies on the effects of smoking on cerebral perfusion and metabolism: basic studies with in vivo tracer methods.

In order to examine the effects of smoking on the central nervous system, we applied the radionuclide method to study the in vivo behavior of nicotine and the effects of nicotine on cerebral perfusion and metabolism. Biodistribution studies with optical isomers of carbon-11 labeled nicotine showed greater uptake and prolonged retention of (S)-nicotine in the brain with competitive inhibition by cold nicotine, suggesting the possibility of functional assessment and imaging of nicotinic receptors in human brain. Senescence accelerated model mouse, which was reported to show age related deterioration of memory, demonstrated decreased accumulation of nicotine in the brain. Intravenous injection of nicotine revealed markedly increased cerebral glucose metabolism with regional differences, while it slightly reduced cerebral blood flow. These results suggest that in vivo studies with radiolabeled tracers will play a significant role not only in clarifying the effects of smoking or nicotine but also in understanding the mechanism of interaction between neuronal function and cerebral perfusion and metabolism.

Animals↗

An artificial amino acid radiopharmaceutical for single photon emission computed tomographic study of pancreatic amino acid transports 123I-3-iodo-alpha-methyl-L-tyrosine.

123I-3-iodo-alpha-methyl-L-tyrosine (123I-L-AMT) was selected and its characteristics on pancreas accumulation, metabolic selectivity and metabolic stability of 125I-L-AMT were studied. The studies on rat tissue slice as well as mouse biodistribution proved very high accumulation of 125I-labeled L-AMT in the pancreas, which was remarkably inhibited by the active transport inhibitor, ouabain. 125I-L-AMT does not enter into protein synthesis and general amino acid catabolism. Moreover, 125I-L-AMT was very stable against enzymatic deiodination. Thus, the above studies indicated that the 123I-labeled L-AMT was an "artificial amino acid" radiopharmaceutical to be used for the selective measurement of the membrane amino acid transport rate in the pancreas.

Amino Acids↗

62Cu-labeled bifunctional radiopharmaceuticals with metabolizable ester groups.

Generator-produced positron emitting 62Cu-labeled bifunctional radiopharmaceuticals with metabolizable ester groups were synthesized and evaluated for their bifunctionality: the Cu chelating ability and the biochemical reactivity of the ester groups. In vitro studies showed high stability of the Cu chelate site (4,4-dimethyldithiosemicarbazone structure) and enzymatic hydrolysis of the ester site (ethylester or acetylester). The 62Cu-labeled compounds showed in vivo behavior which may be due to their ester hydrolysis.

Animals↗

Application of the new zinc-62/copper-62 generator: an effective labeling method for 62Cu-PTSM.

A potential PET flow tracer, 62Cu-labeled pyruvaldehyde bis(N4-methylthiosemicarbazone) (62Cu-PTSM), was prepared using a new 62Zn/62Cu generator. With this 62Cu-labeling method based on a ligand exchange reaction, 62Cu-PTSM was quantitatively obtained by simple mixing of the generator eluate, 62Cu-glycine and PTSM solution for a few seconds. The glycine contained in the 62Cu-PTSM injectate had no significant effect in mouse biodistribution studies. The PET studies of 62Cu-PTSM showed brain images that were not visualized by 62Cu-labeled albumin (a plasma pool tracer), in the dog cranium.

Animals↗

Investigation of radiopharmaceuticals for pancreatic imaging: accumulation of amines in the pancreas.

To develop radiopharmaceuticals for pancreatic imaging, radioiodinated ethyl benzene derivatives containing various functional groups (amino, carboxyl, and methyl groups) were synthesized and the effects of these functional groups were compared in vitro and in vivo. At 2 min after intravenous injection, the amino derivative, 2-(4-iodophenyl)-N,N-dimethyl ethylamine, displayed about twice the pancreatic uptake and a more than 8-fold higher pancreas/liver ratio than the carboxyl and methyl derivatives. This high and selective in vivo accumulation on the amino derivative in the pancreas was well supported by in vitro studies on the uptake by pancreatic tissue slices. The mechanism promoting pancreatic accumulation of radiopharmaceuticals with an amino group is also discussed.

Amines↗

[Anthracycline cardiotoxicity evaluated by digitized M-mode echocardiography].

Ten patients with malignant diseases whose mean age was 20.0 +/- 13.2 years received anthracycline derivatives therapy and were evaluated for their left ventricular systolic and diastolic functions by computer-assisted digitized M-mode echocardiography. Fractional shortening (%FS), a parameter of systolic function, was measured. The first derivative of left ventricular dimension change (peak LV dD/dt), posterior wall thinning (peak LVPW thinning rate) and interventricular septum thinning (peak IVS thinning rate) were used as indices of diastolic function. Blood pressure (BP) was measured noninvasively at the end of the echocardiographic examination and hemoglobin concentration (Hb) was measured on the same day. These examinations were performed immediately before administration of anthracycline and one week and one month after the last administration. Statistical analyses were performed using the Student's t-test. The mean BP, HR, LVDd, LVDs, LVPW and IVS remained unchanged following the drug administration. %FS did not change significantly; 36.8 +/- 6.3%, before the administration, 35.3 +/- 6.5%, one week after the administration, and 36.5 +/- 5.1%, one month after the administration. Peak LVdD/dt and the peak LVPW thinning rate decreased appreciably from 4.46 +/- 1.10 to 3.76 +/- 1.08, and from 7.99 +/- 1.55 to 6.41 +/- 1.04, respectively, one week after the administration. The peak IVS thinning rate decreased from 3.54 +/- 0.81 to 2.99 +/- 0.79 after one week (p < 0.01). All of these values returned to the control levels in one month after the drug administration. We concluded that the indices of left ventricular diastolic function were more sensitive for detecting cardiac impairment than those of systolic function during the course of anthracycline therapy.

Adolescent↗

High myocardial accumulation of radioiodinated digoxin derivative: a possible Na,K-ATPase imaging agent.

In view of the high binding ability of cardiac glycosides to the myocardial Na,K-ATPase, radioiodinated digoxin derivatives were surveyed as candidates for myocardial imaging, with particular emphasis on the noninvasive monitoring of cardiac glycoside therapy. Among the radioiodinated digoxin derivatives surveyed, 125I-digoxin-iodohistamine(bis(O-carboxymethyloxime)) showed the highest accumulation in the myocardium and similar binding ability to Na,K-ATPase as digoxin itself against ouabain displacement, as indicated by in vivo and in vitro studies. Based on these results, 123I labeling of digoxin-histamine(bis(O-carboxymethyloxime)) and imaging in a dog demonstrated uptake in the myocardium.

Animals↗

Regional metabolic abnormality in relation to perfusion and wall motion in patients with myocardial infarction: assessment with emission tomography using an iodinated branched fatty acid analog.

The clinical usefulness of single-photon tomography using both a beta-methyl-branched fatty acid analog, 123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) and 201TI was assessed in 4 normal subjects and 28 patients with myocardial infarction. A homogeneous distribution of the tracer in the left ventricular myocardium was observed in each normal subject. BMIPP uptake was decreased compared to 201TI (discordant) in 17/28 patients (61%) and in 49/196 myocardial segments (25%). Such discordant BMIPP uptake was observed more often in areas of acute myocardial infarction (59% at less than or equal to 4 wk versus 31% at greater than 4 wk after onset) (p less than 0.01) and areas supplied with revascularized arteries (74% for revascularized versus 28% for nonrevascularized areas) (p less than 0.01). In addition, the discordant BMIPP uptake was seen more often in the segments exhibiting a wall motion score lower than the perfusion score (46%) in comparison to segments showing a similar decrease in both the wall motion and perfusion scores (12%) (p less than 0.01). Thus, BMIPP imaging may play a major role in increasing our understanding of the relationship between perfusion and wall motion, particularly in patients with acute myocardial infarction and those who received revascularization therapy.

Fatty Acids↗

A strategy for the study of cerebral amino acid transport using iodine-123-labeled amino acid radiopharmaceutical: 3-iodo-alpha-methyl-L-tyrosine.

We examined the brain accumulation of iodine-123-iodo-alpha-methyl-L-tyrosine (123I-L-AMT) in mice and rats. I-L-AMT showed high brain accumulation in mice, and in rats; rat brain uptake index exceeded that of 14C-L-tyrosine. The brain uptake index and the brain slice studies indicated the affinity of I-L-AMT for carrier-mediated and stereoselective active transport systems, respectively; both operating across the blood-brain barrier and cell membranes of the brain. The tissue homogenate analysis revealed that most of the accumulated radioactivity belonged to intact I-L-AMT, an indication of its stability. Thus, 123I-L-AMT appears to be a useful radiopharmaceutical for the selective measurement of cerebral amino acid transport.

Amino Acids↗

An approach for immunoradiometric assay with metallic radionuclides: gallium-67-deferoxamine-dialdehyde starch-IgG.

Radiogallium (Ga) labeling of an immunoglobulin-G-deferoxamine conjugate (DF-IgG) to a high-specific radioactivity was performed to allow the development of a radiometallic immunoradiometric assay (IRMA) system. To increase the specific radioactivity of Ga-DF-IgG, we used dialdehyde starch (DAS) as a multi-site spacer for the binding of DF to IgG. Six DF molecules bound to each IgG molecule after DAS conjugation. DF-DAS-IgG was then labeled with the previously reported 67Ga labeling solution, producing labeled IgG with a specific radioactivity of 11,766 MBq/mg IgG. Using this method, we labeled an anti-CA125 tumor-associated antigen monoclonal antibody (130-22), allowing the first application of 67Ga-DF-DAS-IgG to an IRMA system. With this system, a higher sensitivity could be obtained than with 125I IRMA. In addition, a very high correlation (r = 0.995) was obtained between serum CA125 levels as determined by 67Ga IRMA and 125I IRMA. Gallium-67-labeled antibodies with a high-specific radioactivity appear to hold promise for use in highly sensitive radioassay systems.

Antigens, Tumor-Associated, Carbohydrate↗

Problems of [S-methyl-11C]-L-methionine as a protein synthesis marker in the pancreas.

To evaluate the possibility of [S-methyl-11C]-L-methionine as a protein synthesis marker in the pancreas, the effect of various labeling positions in the accumulation and metabolism of 14C-labeled L-methionines (S-methyl-14C, 1-14C and 3,4-14C) was studied. In mouse biodistribution studies, the methionines showed differing patterns of labeling position-dependent pancreatic accumulation. In the case of [S-methyl-14C]-L-methionine, protein-incorporation and methyl-transformation equally served as retention mechanisms in the pancreas, indicating [S-methyl-11C]-L-methionine's unsuitability as a pancreatic protein synthesis marker. For such purposes, [1-11C]-L-methionine is considered more suitable.

Animals↗

Monoiodo-D-tyrosine, an artificial amino acid radiopharmaceutical for selective measurement of membrane amino acid transport in the pancreas.

Using 11C-labeled natural amino acids, the functional diagnosis of tissue metabolism has been actively studied. Our interest has been focused on developing a clinically available 123I-labeled artificial amino acid with a single metabolic function. For this study, [123I]3-iodo-D-tyrosine ([123I]D-MIT) was selected. In vitro and in vivo studies using 125I-labeled D-MIT indicated that it showed a high pancreatic accumulation, selective affinity for membrane active transport systems, and was stable against enzymatic deiodination. A canine scintigraphic study using 123I-labeled D-MIT and kinetic analysis showed that it behaved as an "artificial amino acid" radiopharmaceutical with selective membrane amino acid transport affinity in the pancreas.

Amino Acids↗

62Cu-labeling of human serum albumin-dithiosemicarbazone (HSA-DTS) conjugate for regional plasma volume measurement: application of new 62Zn/62Cu generator system.

62Cu-Labeling of human serum albumin-dithiosemicarbazone (HSA-DTS) conjugate was performed using a newly developed 62Zn/62Cu generator system. HSA-DTS was easily labeled with 62Cu, by simple mixing with 62Cu-generator eluate. In vivo blood clearance of 62Cu-HSA-DTS was similar to 131I-HSA, indicating the high applicability of 62Cu-HSA-DTS as a method for plasma volume measurement. In a positron emission tomography study of a dog, a clear plasma pool image of the head region was obtained.

Animals↗

Ga-labeling of immunoglobulin G with high specific radioactivity.

To obtain radiogallium labeled immunoglobulin G with a high specific radioactivity for in vitro use, a 67Ga source was purified by extraction from 67Ga-gallium citrate with butyl acetate, and a 67Ga-labeling solution was produced. This solution was then used to label a deferoxamine-immunoglobulin G conjugate. Both a very high specific radioactivity (872 +/- 56 MBq/mg) and a high labeling efficiency (94.0%) were achieved.

Gallium Radioisotopes↗

Clinical application of echocardiographic imaging to diagnosis of coronary artery disease.

Ergometer two-dimensional echocardiography was performed in 28 subjects complaining of chest pain but without myocardial infarction. Sequential ergometer loading was initiated at 50 or 75 watts, and increased in several stages. Apical four-chamber view two-dimensional echocardiograms were recorded onto video tape, and video images were converted into digital computer signals. After cine-loop display, computer image processing included noise reduction and edge enhancement, M-mode measurements were made at a designated level on the two-dimensional echo images. Wall motion was also analyzed directly from the two-dimensional echo images, using an auto-edge detection method. The derived data were compared with results from coronary angiograms. No echo abnormality was observed at rest, whereas during exercise wall motion was depressed at the diseased site of the angiogram; the amplitude of excursion and the changes in systolic and diastolic velocity were disturbed at the septum in LAD-involved patients, and in the posterolateral wall in both Cx and RCA patients. The imaging success rate using the computer-aided analysis was found to be 92.9%. Sensitivity for diagnosis of coronary artery disease was 82.1% and specificity 89.3%. Ergometer two-dimensional echocardiography with assisted computer image processing appears to be one of the most valuable tools for clinical real time evaluation of coronary artery disease.

Coronary Disease↗