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Biomedical subjects

Y Fujibayashi

Publications and source records attributed to Y Fujibayashi.

At least 109 records · Page 6Linked to original sources
PubMed1990

[Radiolabeling and biodistribution of 62Cu-dithiocarbamate--an application for the new 62Zn/62Cu generator].

The newly developed 62Zn/62Cu generator system has made available the production of the short-lived 62Cu (T1/2 = 9.8 min) positron radionuclide, eluted as 62Cu-glycine. In the search for 62Cu labeled radiopharmaceuticals for positron CT (PET) brain diagnostic studies, two ligands N,N-diethyl- and N,N-dimethyl-dithiocarbamic acid (DDC and DmDC) were selected, based on their Cu chelating abilities and the neutral lipophilic character of their copper chelates. In the present work, an in vitro study with non-radioactive Cu-glycine showed that both ligands easily formed the stable, neutral Cu-DDC and Cu-DmDC chelates (1:2 metal-ligand complexes) based on the ligand exchange reaction. Then the 62Zn/62Cu generator eluate, the 62Cu-glycine was used for the radiolabeling of DDC and DmDC. The following HPLC analysis revealed that the ligand exchange reaction proceeded rapidly; the radiochemical purities of 62Cu-DDC and 62Cu-DmDC were extremely high (non-detectable 62Cu-glycine) and both chelates were more lipophilic than 62Cu-glycine. The mouse biodistribution of both radiolabeled compounds, 62Cu-DDC and 62Cu-DmDC indicated a brain accumulation of 2.8 and 5.3 times higher than 62Cu-glycine, 15 min post injection, respectively. The brain accumulation observed with both 62Cu-DDC and 62Cu-DmDC might be due to their stable, neutral and lipophylic character; the latter enhanced by the presence of the methylated side chains. The gathered results indicated the applicability of dithiocarbamic acid derivatives in the production of new 62Cu-labeled compounds using the 62Zn/62Cu generator system based on the ligand exchange reaction with 62Cu-glycine eluate. Further studies with Cu-dithiocarbamic acid derivatives for development of new generator-produced 62Cu positron radiopharmaceuticals can be recalled.

Animals↗
PubMed1990

[Ischemic heart disease evaluated using dipyridamole-stress two-dimensional echocardiography].

Dipyridamole-stress two-dimensional echocardiography (2DE) was performed in 25 subjects, 14 with stenotic and 11 with normal coronary arteries by coronary angiography, to assess the sites and severity of coronary artery stenosis noninvasively. Dipyridamole was administered intravenously with a dose of 0.56 mg/kg for 4 min. 2DE was recorded at the lower papillary muscle level and the percent fractional area change (% FAC) of the left ventricular segments was computed (FV). In all cases with an echocardiographic regional wall motion abnormality in the interventricular septum, a significant stenosis (greater than or equal to 75%) was documented angiographically in the left anterior descending coronary artery (LAD). In seven of eight patients with a segmental abnormality in the inferolateral wall, a significant stenosis was observed in the left circumflex coronary artery (Cx). The sensitivity and specificity of dipyridamole-stress echocardiography were 100% and 92%, respectively, for an LAD stenosis, and and 87.5% and 71%, respectively, for a Cx stenosis. The segmental wall motion abnormality induced by dipyridamole resolved within four to five min after terminating the infusion in patients with coronary artery narrowing of 75%; whereas, it persisted up to six to seven min in patients with 90% narrowing. There was no improvement in the LV wall motion 15 min after the termination of the infusion in patients with severe narrowing (99%). In conclusion, dipyridamole-stress echocardiography proved to be one of the most useful methods, not only for detecting coronary artery disease, but for predicting the severity and for localizing the sites of lesions as well.

Analysis of Variance↗
PubMed1990

Myocardial accumulation of iodinated beta-methyl-branched fatty acid analogue, iodine-125-15-(p-iodophenyl)-3-(R,S)methylpentadecanoic acid (BMIPP), in relation to ATP concentration.

To clarify the relationship between the myocardial accumulation of 125I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and intracellular adenosine-5'-triphosphate (ATP) content, the effect of 2,4-dinitrophenol (DNP, an electron transport uncoupler) on myocardial BMIPP accumulation was studied, in comparison with that of thallium-201-chloride (201Tl-Cl). In the mouse myocardium, DNP decreased the intracellular ATP and ADP levels, without affecting either acyl-CoA synthetase activity or the level of CoA-SH. Following treatment with DNP, decreases in myocardial BMIPP accumulation correlated well with those of ATP, while 201Tl-Cl showed slightly increased accumulation in the myocardium. Thus, in some diseases, BMIPP may be useful in evaluating myocardial ATP levels.

2,4-Dinitrophenol↗
PubMed1990

[Fatty acid metabolism using C-11 palmitate: (1). Resting study].

Serial dynamic images were obtained at rest following intravenous injection of 185-370 MBq (5-10 mCi) of 11C-palmitate for 40-50 minutes in 3 normal subjects and 6 patients with coronary artery disease. Due to the rapid clearance of activity from the blood, myocardial images were observed within 5 minutes after the injection in each case. The time activity curve of each myocardial region indicates biexponential clearance. The early clearance half time (Te 1/2) was similar in normal myocardium (18.8 +/- 6.0 min), ischemic myocardium (19.3 +/- 5.8 min) and infarcted myocardium (15.5 +/- 6.0 min). The late clearance half time (Tl 1/2) was also similar among these groups (81.4 +/- 36.0, 66.9 +/- 25.7 and 57.8 +/- 37.4, respectively). However, the residual fraction (%E) was slightly lower in the ischemic myocardium (19.6 +/- 11.0%) (p less than 0.05), indicating decreased beta oxidation in the former. Although positron emission tomography using 11C-palmitate may permit assessment of fatty acid metabolism, the parameters in this study were greatly fluctuated at rest among the normal, ischemic and infarcted myocardium. Further investigations under various interventions may be warranted.

Carbon Radioisotopes↗
PubMed1989

Design, synthesis and 64Cu labeling of fatty acid analogs containing dithiosemicarbazone chelate.

For the development of 62Cu labeled fatty acid analogs, two fatty acid analogs, containing dithiosemicarbazone (DTS) molecule as the 62Cu coordinating site, were designed and synthesized: a fatty acid analog containing DTS molecule at the omega-position, (a) the 12,13-dioxotetradecanoic acid di(N-methyl-thiosemicarbazone) (FA-DTS), and an omega-phenyl fatty acid analog containing DTS molecule at the para-position, (b) the p-carboxyundecylphenylglyoxal-di (N-methylthiosemicarbazone] (PFA-DTS). FA-DTS was synthesized by the reaction of ethyl diethoxyacetate with ethyl 11-bromonundecanate by successive decarboxylation and hydrolysis and final condensation with N-methylthiosemicarbazide. PFA-DTS was synthesized by the Friedel-Craft acylation of ethyl 11-phenylundecanate, selenium oxidation of the acetophenone derivative, followed by the condensation with N-methylthiosemicarbazide. Radiolabeling of FA-DTS and PFA-DTS with [64Cu]copper acetate was simple, rapid and quantitative. When injected into mice, both compounds were distributed and retained in the myocardium. These results offer a good basis for further development of 62Cu labeled fatty acid analogs.

Animals↗
PubMed1989

[A noninvasive study on characteristics of the left ventricular function in elderly hypertensive patients].

To characterize the left ventricular (LV) systolic and diastolic function in elderly hypertensives, mechano-and echocardiography was performed in 27 elderly patients more than 65 years of age (20 hypertensives and 7 normotensives) and 46 middle-aged patients (34 hypertensives and 12 normotensives). In normotensives, a positive correlation was found to exist between age and blood pressure, LV wall thickness, II-RF interval and the A/E ratio, whereas the correlation of age to systolic parameters such as ET/PEP and EF was absent. This suggests that the LV diastolic function was impaired progressively by aging with preservation of the LV systolic function. In elderly hypertensives, LV systolic function was deteriorated and the A/E ratio increased as diastolic blood pressure became elevated. The A/E ratio also increased in this group as compared with that in middle-aged hypertensives, although the differences was not statistically significant. Unlike those in middle-aged hypertensives, the indices of LV function except the elevated blood pressure and the increased cardio-thoracic ratio were not significantly different between hypertensive and normotensive elderly patients. This might be because of the wide range of normal values in elderly persons due to the various degrees of atherosclerotic changes and other pathophysiologic factors, which might have masked obvious characteristics of hypertension in elderly hypertensives.

Adult↗
PubMed1989

A new zinc-62/copper-62 generator as a copper-62 source for PET radiopharmaceuticals.

A new 62Zn/62Cu generator system was designed to provide a readily available 62Cu source for positron emission tomographic radiopharmaceuticals, based on the differences of complex formation between Zn and Cu. Noncarrier added 62Cu was selectively eluted as a glycine complex from 62Zn-adsorbed cation-exchange resin (CG-120, Amberlite), when a glycine solution (200 mM) was used as the eluant. The elution efficiency and radionuclidic purity of 62Cu were 70% and greater than 99.9%, respectively. Copper in glycine solution showed rapid complex formation with dithiosemicarbazone, which is one of the established Cu-binding agents for bifunctional chelating radiopharmaceutical.

Chromatography, High Pressure Liquid↗
PubMed1986

A new approach toward a pancreas-seeking zinc radiopharmaceutical. I. Accumulation of 65Zn-amino acid and aminopolycarboxylic acid complexes in pancreatic tissue slices.

There have been many attempts to develop zinc-containing radiopharmaceuticals for use as pancreas-seeking agents, but little consideration has been given to Zn-complex structure as being a factor that contributes to Zn utilization by the pancreas. In the present study, various ligands having N-O donor groups (amino acids and aminopolycarboxylic acids) with variable numbers of coordination sites (2-6) were investigated with regard to the coordination of the radiometal Zn. As an experimental model, freshly prepared slices of rat pancreas were studied, and Sephadex-column chromatography analysis was also performed. The structure and stability of Zn complexes were found to affect the accumulation of Zn in pancreas slices. In particular, the administration of tetradentate ligand complexes of 65Zn-ethylenediamine-N,N'-diacetic acid (EDDA) and 65Zn-nitrilotriacetic acid (NTA) resulted in high Zn utilization in the pancreas. Also, Zn complexes of intermediate stability (as demonstrated by elution behavior at Sephadex-column chromatography) produced the best results.

Amino Acids↗
PubMed1986

A new approach toward a pancreas-seeking zinc radiopharmaceutical. II. 62Zn-EDDA (ethylenediamine-N,N'-diacetic acid) for pancreas PCT imaging.

The functionality of various zinc complexes of amino acid derivatives as a zinc radiopharmaceutical for pancreas PCT imaging was tested using 65Zn, which has a long half-life, and 62Zn, which has a short half-life. Because of the favorable results obtained in previous in vitro pancreas section studies, the ability of those Zn complexes to retain their integrity in the presence of blood serum or in living organisms was screened using Sephadex column chromatography and mice biodistribution studies. A relationship between the structure and stability of Zn complexes played a determining role on the in vivo availability of Zn for the pancreas or liver. Among the Zn complexes tested, the tetra-coordinated structure of the Zn-EDDA complex at an equimolar ratio showed proper accumulation in the pancreas, inducing an appropriate pancreas PCT image in the dog with the positron emitter 62Zn-EDDA administered at 1 mg Zn/kg body weight.

Animals↗
PubMed1986

62Zn-EDDA: a radiopharmaceutical for pancreatic functional diagnosis.

As Zn is closely associated with the exocrine and endocrine functions of the pancreas, exploitation of Zn metabolism for anatomical and functional diagnosis was conceived, namely with the recent availability of positron emitting 62Zn (t1/2 = 9 h). In the present paper, response changes in Zn biodistribution (mice) and Zn excretion through the pancreatic duct (rats) due to the stimulation of gastro-intestinal hormones like secretin, CCK-PZ (exocrine stimulation) and glucose (endocrine stimulation) were studied. Under these stimuli, the pancreatic secretion of radioactive Zn through cannulated pancreatic duct showed increased Zn secretion only under the CCK-PZ effect, 3 h post 65Zn (t1/2 = 270 d) injection. Tissue biodistribution in mice pre-injected with 65Zn showed pancreas specific decrease of radioactive Zn whenever a gastro-intestinal hormone was post-administered, whereas the glucose effect was negligible. Thus, the effective mobilization of the injected radioactive Zn, upon exocrine stimulation, represented by CCK-PZ, favored the exploration of a functional study of the pancreas with the positron computed tomograph (PCT) using short lived nuclide labeled 62Zn-EDDA in dog. Evidence of the applicability of this system in regional function studies of the pancreas was obtained. Demonstration of Zn participation in the exocrine function of the pancreas in-vivo holds considerable promise for diagnosis of pancreatic diseases.

Animals↗
PubMed1986

Effects of staged versus sudden reperfusion after acute coronary occlusion in the dog.

Sudden and staged reperfusion after experimental coronary artery occlusion was studied in relation to recovery of cardiac function and postreperfusion arrhythmias. Eighteen closed chest dogs with 3 hour intracoronary balloon occlusion of the proximal left anterior descending coronary artery were studied using two-dimensional echocardiography over a period of 3 weeks after reperfusion. Nine dogs had sudden reperfusion by abrupt balloon deflation. In nine other dogs reperfusion was staged with partial reflow (20 ml/min) for 2 hours through the central lumen of the catheter during persisting intracoronary balloon inflation, followed by balloon deflation and full reperfusion. Within the first 30 minutes of sudden reperfusion, ischemic zone end-diastolic wall thickness increased significantly, from 6.8 +/- 0.3 mm at 3 hours of occlusion to 10.2 +/- 2.6 mm (p less than 0.05). In contrast, at 30 minutes of partial reflow, wall thickness was 7.5 +/- 0.7 versus 6.8 +/- 0.7 mm at 3 hours of occlusion (NS). A small temporary increase in end-diastolic wall thickness was noted when full reflow was established after 2 hours of staged reperfusion. However, wall thickness was normal on the first day in the staged reperfusion series, while sudden reperfusion delayed recovery to 7 days. Function of the ischemic zone failed to improve substantially until day 3 after sudden reperfusion, whereas it improved consistently starting as early as 30 minutes after institution of the staged reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1986

Attenuation correction in echocardiography.

A commercial two-dimensional echo unit, modified to permit digital acquisition (2.2 MHz) of echo signals prior to time-gain-compensation (TGC), was ratiometrically calibrated. Simulating the TGC in software, we demonstrated improvements in image quality as compared to conventional video methods. A path-dependent attenuation correction (PDAC) algorithm, utilizing the gray level image statistics to assign one of three attenuation coefficients (for chest, myocardium or blood) to each image pixel, was then developed. Using it on left ventricular (LV) short axis images obtained in nine healthy closed chest dogs, we demonstrated that the backscatter intensity at end diastole (ED) was 2.0 +/- 0.5 dB (mean +/- SEM) higher (p less than 0.01) than at end systole (ES), in circumferential segments of the myocardium oriented anteriorly and posteriorly, relative to the transducer. In seven of the dogs, subsequently occluded for one hour in the anterior descending branch of the left coronary artery (LAD), this normal phasic myocardial backscatter (PMB) variation decreased or was reversed in ischemic segments, relative to preocclusion values, suggesting utility of the method for sequential study of myocardial ischemia and its treatment.

Animals↗
PubMed1986

A radiopharmaceutical for pancreatic exocrine functional diagnosis: 62Zn-EDDA metabolism in pancreas.

The metabolic pathway of radioactive 62Zn-EDDA (ethylenediamine-N,N'-diacetic acid), in the exocrine pancreas was studied with respect to that of endogenous Zn. In pancreatic duct cannulated dog, the secretion of intravenously injected exogenous 62Zn into pancreatic juice increased under the stimulation of CCK-PZ (pancreatic protein secretion stimulating hormone), which closely correlated to endogenous Zn. Moreover, in pancreatic juice, 62Zn as well as endogenous Zn was selectively bound to Zn-metalloenzymes, carboxypeptidase A and B. These results demonstrated the close correlation between the endogenous and the exogenously-administered Zn (62Zn-EDDA), as well as the high availability of 62Zn-EDDA as a marker of pancreatic function for the follow up of carboxypeptidase metabolism.

Animals↗