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Biomedical subjects

H Saji

Publications and source records attributed to H Saji.

At least 145 records · Page 8Linked to original sources

Measurement of arterial time-activity curve by monitoring continuously drawn arterial blood with an external detector: errors and corrections.

Accurate description of the arterial time-activity curve (ATAC) is of paramount importance in quantitative determination of the regional cerebral blood flow (rCBF) using positron tomography following bolus i.v. injection of 0-15 labeled water. Frequent manual sampling from an arterial catheter does not permit sampling in less than 5-sec intervals and runs the risk of missing the arrival time or the peak count. A continuous ATAC monitoring system has been developed. This system consists of a single bismuth germinate detector in a lead shield and a constant-flow aspirator. The arterial blood was drawn continuously from a catheter within the brachial artery into an extended tube and its activity was monitored by the detector as the detector time-activity curve (DTAC). Comparison with the manual sampling from the contralateral brachial artery in the same run revealed that the DTAC differed from the manual sampling not only in delayed arrival but also in the shape of the curve, which was dispersed because of viscosity and the width of the detector field of view. However, deconvolution of DTAC using the experimentally obtained system step response provided an accurate arterial time course, which successfully filled in the gaps of the manual sampling. Moreover, water and blood showed different dispersion in the step response, suggesting that the system function should be determined using blood or a fluid of similar hydrodynamic nature.

Arteries↗

A new subtraction method for obtaining myocardial perfusion images with oxygen-15 water and positron emission tomography.

The myocardial positron emission tomograms which are obtained during the perfusion phase following bolus injection of O-15 water (H2(15)O) intravenously require subtraction of the blood pool activity overlaid upon the myocardium. Subtraction has been carried out using the blood pool images obtained in the same position following single inhalation of O-15 labeled carbon monoxide gas (C15O). However, because a difference in activity exists between the left ventricular (LV) cavity and the right ventricular (RV) cavity, simple subtraction of the LV cavity activity using C15O blood pool images induced significant over-subtraction in the right-side heart including the interventricular septum and RV wall. We developed a new method, "two-component subtraction," in which the C15O blood pool images were decomposed into the right-side and left-side components using the early phase images of the H2(15)O dynamics under the assumption that the whole activity of that phase was distributed in the right-side heart homogeneously. Thus we subtracted the blood pool spillover from RV and LV separately. This method provided myocardial perfusion images of high quality which were well correlated with N-13 ammonia images.

Heart↗

Value and limitation of stress thallium-201 single photon emission computed tomography: comparison with nitrogen-13 ammonia positron tomography.

The diagnostic value of exercise 201Tl single photon emission computed tomography (SPECT) for assessing coronary artery disease (CAD) was comparatively evaluated with exercise [13N] ammonia positron emission tomography (PET). Fifty-one patients underwent both stress-delayed SPECT imaging using a rotational gamma camera and stress-rest PET imaging using a high resolution PET camera. Of 48 CAD patients, SPECT showed abnormal perfusion in 46 patients (96%), while PET detected perfusion abnormalities in 47 (98%). The sensitivity for detecting disease in individual coronary arteries (greater than 50% stenosis) was also similar for SPECT (81%) and PET (88%). When their interpretations were classified as normal, transient defect, and fixed defect in 765 myocardial segments, SPECT and PET findings were concordant in 606 segments (79%). However, 66 segments showed a fixed defect by SPECT but a transient defect by PET, whereas there were only nine segments showing a transient defect by SPECT and a fixed defect by PET. PET identified transient defects in 34% of the myocardial segments showing a fixed defect by SPECT. We conclude that both stress SPECT and PET showed high and similar sensitivities for detecting CAD and individual stenosed vessels. Since stress-delayed SPECT with single tracer injection detected fewer transient defects, it may underestimate the presence of myocardial ischemia, compared with high resolution PET imaging with two tracer injections.

Adult↗

In vitro evaluation of radioiodinated butyrophenones as radiotracer for dopamine receptor study.

Radioiodinated butyrophenone compounds are attracting the interest of those working on dopamine receptor studies; structure-activity relationship study has revealed the ortho position of the p-fluorobutyrophenone moiety as a very plausible iodination site. Various synthesized butyrophenones iodinated at the ortho position of p-fluorobutyrophenone moiety, 2'-iodohaloperidol (2'-IHP), 2'-iodotrifluperidol (2'-ITP) and 2'-iodospiperone (2'-ISP) were tested for their abilities to inhibit 3H-spiperone (SP) binding for the dopamine (D-2) receptor, together with reference compounds (SP, haloperidol(HP) and 4-iodospiperone (4-ISP]. The order of binding affinity of the tested compounds was SP greater than 2'-ISP greater than HP greater than 4-ISP greater than 2'-IHP greater than 2'-ITP. Whereas, the serotonin (S-2) receptor binding affinity of SP and its iodinated analogues were in the order of SP much greater than 4-ISP greater than 2'-ISP. Furthermore, in the saturation binding study using the striatal membrane preparations, the 2'-ISP displayed a KD of 0.25 nM with maximum number of binding site Bmax of 210 fmol/mg protein. These data indicated the 2'-ISP as holding high affinity for dopamine receptors and a low affinity for serotonin receptors. Thus, the 125I-2'-ISP was a very potent radioligand for in vitro dopamine (D-2) receptor studies, and 123I-2'-ISP holds very promising characteristics as for in vivo dopamine receptor studies, as well.

Animals↗

Radioiodinated 2'-iodospiperone: a new radioligand for in vivo dopamine receptor study.

In vivo dopamine receptor binding of the newly synthesized ligand, 125I-2'-iodospiperone (125I-2'-ISP), was studied in mouse brain. The highest accumulation was found in the striatum. Analysis of the striatal homogenate showed the 125I-2'-ISP to be metabolically stable. Furthermore, this striatal binding was saturable and displaced only by dopaminergic drugs. On the other hand, the accumulation in the cortex was as low as that of the cerebellum and uneffected by the administration of serotoninergic drugs and dopaminergic drugs; results assessed by macroautoradiographic studies. Thus, the newly synthesized 125I-2'-ISP presented high affinity for dopamine receptors in vivo and therefore, holds great potential for the in vivo dopamine receptor studies, provided 123I becomes readily available.

Animals↗

Platelet factor XIII is activated by calpain.

The action of calpain (EC 3.4.22.17; Ca2+-dependent cysteine proteinase) on platelet factor XIII has been studied. Calpain I activated platelet factor XIII up to 76% of the maximum level observed with thrombin. Activation was accompanied by the limited proteolysis of the a subunit of platelet factor XIII to produce a 76 kDa fragment which was comparable to the proteolytic product by thrombin. Activation of platelet factor XIII by calpain was inhibited by EDTA, leupeptin, and endogenous calpain-specific inhibitor calpastatin. These findings suggest that calpain is responsible for the intracellular activation of platelet factor XIII.

Blood Platelets↗

Detection of coronary artery disease with 13N-ammonia and high-resolution positron-emission computed tomography.

In order to evaluate the detectability of coronary artery disease (CAD) with positron-emission computed tomography (PET), we performed 13N-ammonia myocardial PET scanning at rest and with exercise loading in 20 normal subjects and 40 patients with CAD, by means of a high-resolution, multi-slice, whole-body PET scanner. Myocardial PET scanning was performed 3 minutes after injection of 13N-ammonia at rest and during exercise. The circumferential profile analysis of resting PET images revealed regional hypoperfusion in 96% of CAD patients with previous myocardial infarction and in 29% of those without infarction. Exercise PET studies showed high sensitivity (93%) in detecting CAD without myocardial infarction, whereas no abnormal hypoperfusion was detected in normal subjects. Segmental analysis of regional myocardial perfusion with exercise stress identified 67 of 75 stenosed vessels (89%). We conclude that 13N-ammonia myocardial PET with exercise loading provides high-quality tomographic images of regional myocardial perfusion and is a valuable technique for detecting CAD.

Adult↗

Procurement of radioiodinated glucose derivative and its biological character.

Radiolabeled glucose derivatives are attracting great interest in the clinical field. Development of an analogous substrate labeled with a practical radionuclide, 123I, is most desirable, however, no radioiodine labeled glucose derivative has been reported as being chemically and biologically compatible. Thus, in the present study, a glucose derivative substituted at the C-2 position by a p-iodobenzyl group, a 2-O-(p-iodobenzyl)-D-glucose (IBG) was designed and its synthesis was carried out. A very easy and simple synthetic method was developed, and the obtained IBG showed appropriate purity and stability for its radioiodination. [125I]IBG was obtained by radioisotopic exchange reaction with high radiochemical purity and radiochemical yield, requiring no purification. The good in vivo and in vitro stability and the chemical and biological characteristic displayed by the new [125I]IBG stimulated the measurement of the brain uptake index (BUI). In the presence of glucose, brain uptake inhibition was detected, a good indication of a glucose carrier mediator for the transport of [125I]IBG through the blood-brain barrier, a similar feature to that of [14C]glucose or 3-O-[14C]methylglucose. The newly designed ligand IBG holds good promise for the study of regional cerebral glucose utilization, should the 123I become available.

Animals↗

[Exercise 13NH3-positron emission computed tomography (PET) versus exercise single photon emission computed tomography (SPECT)].

The value of exercise positron emission computed tomography (PET) was determined by comparing it with exercise T1-201 single photon emission computed tomography (SPECT) using graded ergometer exercise in 10 anginal patients with left anterior descending coronary (LAD) involvement (stenosis greater than or equal to 75%) with or without other coronary stenosis. The distribution of N-13 ammonia or T1-201 was determined and expressed as percent count ot the highest count on the circumferential profile curve (CPC) in the transaxial image. Two standard deviations below the mean counts of six normal hearts for PET and ten for SPECT were considered as the lower limit of normal, and these were determined separately during exercise and at rest. The ischemic areas per total myocardial areas (%C), the accuracy in diagnosing coronary involvement and the identification of coronary branch involvement were determined by CPC analysis in three corresponding slices. Regional analyses revealed that accuracy in diagnosing proximal left anterior descending artery (LAD) involvement was higher with PET (9/10) than with SPECT (7/10), but the difference was not statistically significant. The accuracy in diagnosing right coronary or circumflex artery stenosis was 9/10 with PET and 8/10 with SPECT (NS); the %C was significantly higher with PET than with SPECT during exercise (PET: mean +/- SD = 56 +/- 21%, SPECT: 35 +/- 21%, p less than .01) in spite of smaller double products (x10(3] (PET: 18.9 +/- 4.7, SPECT: 23.5 +/- 5.7, p less than .02). Thus, exercise PET was more reliable in evaluating regional ischemia and in semiquantifying the ischemic area in the myocardium.

Ammonia↗

Technetium-99m-labeled monoclonal antibody with preserved immunoreactivity and high in vivo stability.

Recent availability of monoclonal antibodies (MoAb) and their radiolabeling through the use of the bifunctional chelating agents (BCA) have become an alternative procedure for in vivo radioimmunodetection. Using a newly synthesized BCA, a p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone) (CE-DTS), the coupling and technetium-99m (99mTc) labeling of monoclonal IgG against hCG were carried out. In the system presented, factors affecting stability and immunoreactivity were examined. Immunoreactivity of the original IgG (56C) was preserved by conjugating one CE-DTS molecule per molecule of IgG (56C) using the phosphorylazide method, however, 99mTc labeling pH affected the immunoreactivity and limited the 99mTc labeling reaction between pH 4.5 and 6.2. A screening of labeling conditions, such as pH, reaction time, and reducing agent system were then carried out. Technetium-99m-labeled IgG (56C), [99mTc]CE-DTS-IgG (56C), showed good stability upon incubation with mice sera and comparable mice biodistribution to that of indium-111 (111In) DTPA-IgG (56C). Thus, these results indicate the excellent potential of CE-DTS as a BCA for labeling MoAb with 99mTc.

Animals↗

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↗

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↗