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Biomedical subjects

G Westera

Publications and source records attributed to G Westera.

At least 37 records · Page 2Linked to original sources

The elimination rate of 123I-heptadecanoic acid after intracoronary and intravenous administration.

When calculating the elimination rate of radioactivity after the administration of radioiodinated heptadecanoic acid (123I-HDA), background correction is necessary due to the high level of background activity. In the present study, the subtraction method of Freundlieb et al. was investigated on validity. This was done by comparing the half-time values of the elimination rate after intravenous (i.v.) and intracoronary (i.c.) injection. In the latter case, no background correction was necessary. Six patients undergoing cardiac catheterization were studied. Scintigraphy was performed after the injection of 123I-HDA into the left coronary artery and after i.v. injection. Half-time values were calculated from regions of interest drawn over myocardium perfused by the left-anterior descending branch (LAD) and the left circumflex artery (LCX). In the LAD region, the mean half-time value in the i.c. study was 22 min, while in the corrected i.v. study, the mean value was 27 min. In the LCX region, the half-time values were 24 and 33 min, respectively. The background-subtraction procedure proposed by Freundlieb et al. for i.v.-injected 123I-HDA is incomplete, as it resulted in half-time values that were higher than those of the i.c. study.

Arteries

A convenient method for the preparation of 99mTc(V)dimercaptosuccinic acid (99mTc(V)-DMSA).

Tc(IV)-DMSA for kidney scintigraphy has been prepared in acidic solution. Once the labeling is done in basic solution, upon addition of a small amount of NaHCO3, a mixture of 3-4 other DMSA-complexes is formed, presumably containing Tc(V). Kidney uptake in male adult rats of the 99mTc(V)-DMSA is 1.6% injected dose/g (4.9%/total organ) compared to 16.4% injected dose/g (resp. 50.3%/total organ) for 99mTc(IV)-DMSA.

Animals

Myocardial uptake of radioactively labelled free fatty acids.

Structural variations in the carbon chain of free fatty acids influence the uptake of free fatty acids in the myocardium. To enable the use of free fatty acids in nuclear cardiology, various methods of introducing gamma-emitting isotopes have been evaluated. The uptake of various free fatty acids is described and structure-activity relationships deduced.

Animals

Kinetics of radioiodinated heptadecanoic acid and metabolites in the normal and ischaemic canine heart.

This study was undertaken to elucidate if the myocardial elimination rate of the radioactivity after administration of radioiodinated heptadecanoic acid was related to beta-oxidation of the fatty acid or related to washout of free radioiodide. In samples of normal and ischaemic myocardium the distribution of the radioactivity over free radioiodide, heptadecanoic acid and lipids was determined. In normal myocardium the major component was free radioiodide, only a small percentage being heptadecanoic acid. In ischaemic myocardium more radiolabelled lipids were present and less free iodide when compared with normal myocardium. The percentage heptadecanoic acid was slightly increased. It is concluded that radioiodinated heptadecanoic acid behaves like the natural analogues regarding uptake and distribution. However, washout of free radioiodide determines the elimination rate as observed during a scintigraphic study.

Animals

Free fatty acid scintigraphy in patients with successful thrombolysis after acute myocardial infarction.

Twenty-three patients with successful intracoronary thrombolytic therapy in the acute stage of infarction underwent scintigraphy with radioiodinated heptadecanoic acid two weeks after myocardial infarction and three to 12 months later. In patients with normal or slow elimination rates in the infarct area, ejection fractions were significantly higher than in patients with fast elimination (70 +/- 6% vs 47 +/- 13%, P less than 0.05). Consequently, left ventricular damage score was lower in patients with normal and slow elimination rates (1.7 +/- 1.6 vs 4.9 +/- 2.4, P less than 0.05). Repeated scintigraphy showed normalization of the elimination rates in patients with previously slow elimination, except in one patient in whom the elimination rate remained slow, patients with fast elimination rates remained unaltered. It is concluded that scintigraphy with radioiodinated heptadecanoic acid is an appropriate method to assess myocardial viability in patients with successful thrombolytic therapy.

Adult

Metabolic fate of radioiodinated heptadecanoic acid in the normal canine heart.

To clarify the metabolic fate of radioiodinated heptadecanoic acid in myocardium, the time course and distribution of the radioactivity over 131I-heptadecanoic acid, free radioiodide, and various lipids (with incorporated iodoheptadecanoic acid) were determined in normal canine myocardium. In 10 dogs seven biopsy specimens were taken over 30 min after injection of 131I-heptadecanoic acid. The radioactivity in the specimens increased until the fifth minute and decreased thereafter, with a half-time of 36 min. In the fifth minute, 61% of the radioactivity was free iodide, and its curve paralleled the curve of the total radioactivity. As early as the first minute 131I-heptadecanoic acid activity was reduced to 14% and decreased further. Activity of radioiodinated phospholipids, (mono, di, tri)-glycerides, and cholesterol-esters remained constant after an initial increase. These results indicate that immediately after uptake, 131I-heptadecanoic acid is either metabolized, liberating the radioiodide, or stored in lipids. Because the activity of radiolabeled lipids remained constant during the study period and because iodide activity paralleled the total activity in biopsy specimens, it is concluded that in normal myocardium, washout of free radioiodide determines the elimination rate as observed during a scintigraphic study. Thus the elimination rate cannot be related to the beta-oxidation rate as previously supposed.

Animals

Synthesis, receptor binding, and target-tissue uptake of carbon-11 labeled carbamate derivatives of estradiol and hexestrol.

The reaction of ethyl chloroformate with amino compounds has been evaluated as a simple route to carbon-11 labeling of steroid hormone-receptor-based imaging agents. Both a 17 beta-amino analogue of estradiol and an aminoethyl derivative of the nonsteroidal estrogen hexestrol with potential affinity for the estrogen receptor were studied. The unlabeled carbamate derivatives of the amino estrogens were prepared by standard methods, and the 11C-labeled analogues were synthesized from [11C]ethyl chloroformate, generated by purging ethanol with [11C]phosgene. Both carbamates showed weak in vitro binding affinity for the estrogen receptor, and only the 11C-labeled hexestrol exhibited a small but significant estrogen-responsive uterus uptake in immature rats.

Animals

Metabolic consequences of beta-adrenergic receptor blockade for the acutely ischemic dog myocardium.

In an experimental study in 50 dogs the myocardial uptake of free fatty acids (FFAs) after beta-blockade was determined using radioiodinated heptadecanoic acid as a metabolic tracer. All 4 beta-blockers used (metoprolol, timolol, propranolol and pindolol) lowered the uptake of FFAs in the normal canine heart. Uptake of FFAs was also diminished after coronary artery occlusion per se, but administration of beta-blockers exerted little additional influence on the uptake of FFAs. This observation was qualitatively paralleled by the uptake of 201Tl in concomitant experiments. Plasma FFA levels were increased by pindolol (non-selective with intrinsic sympathomimetic activity), not changed by metoprolol (a cardioselective beta-blocking agent) and lowered by timolol and propranolol (both non-selective compounds). The extent of ischemic tissue, as reflected by uptake of iodoheptadecanoic acid and 201Tl, was diminished by metoprolol but not by other beta-blockers. Regional distribution of both tracers, as shown in the endo-epicardial uptake ratios, was hardly influenced by beta-blockade, except for a small increase of 201Tl uptake in non-occluded endocardium. Uptake of 201Tl as well as of iodoheptadecanoic acid in the ischemic area was increased by metoprolol, timolol and propranolol and decreased by pindolol. We conclude that beta-blocking agents confer different effects on myocardial uptake and metabolism of FFAs which might possibly be related to their different inherent properties.

Acute Disease

Determination of myocardial FFA elimination rates by functional images of uncorrected half-time values.

This paper presents an alternative method of demarcating regions of interest over the myocardium after administration of 123I-heptadecanoic acid to patients with coronary artery disease. In a matrix of 32 X 32 pixels the elimination rates of the radioactivity, which are not corrected for background activity, are visualized per pixel in a functional image. The functional image showed areas in the myocardium with high values of uncorrected elimination rates. These areas corresponded with the tracer defects on the scintigram. Corrected elimination rates obtained from regions of interest of functional images were comparable with those of scintigrams. Thus based on functional images of uncorrected elimination rates a reliable, objective determination of regions of interest over normal and abnormal myocardium can be made.

Adult

Myocardial uptake of iodinated free fatty acids and 201Tl in experimental ischemia.

In an experimental study, we evaluated the uptake of (131I)-17-iodo heptadecanoic acid (131I-HDA), (125I)-15-4 (4-iodophenyl) pentadecanoic acid (125I-PPA) and thallium-201 (201Tl) in the dog heart. Twenty dogs were studied and divided into 3 groups: in group A, 10 dogs (4 normal, 6 with coronary artery occlusion) were studied with 131I-HDA and 201Tl; in group B, 5 dogs (with occlusion) received 125I-PPA and 201Tl; and in group C, 5 dogs (with occlusion) were studied with 125I-PPA and 131I-HDA. Two min after administration of the compounds the hearts were excised and stored in formaldehyde. After sectioning of the left ventricle, total uptake was counted and expressed in percentage of injected dose. Uptake in the normal myocardium (group A) was 4.2 +/- 0.6% for 131I-HDA and 4.6 +/- 0.7% for 201Tl; in the occluded dog hearts (group A) we measured values of 2.6 +/- 0.4% for 131I-HDA (p less than 0.001) and 3.4 +/- 0.6% for 201Tl (p less than 0.01). Uptake of 131I-HDA, 125I-PPA and 201Tl in groups B and C was not significantly different: group B, 125I-PPA 2.8 +/- 0.8% and 201Tl 2.5 +/- 0.5%; group C, 125I-PPA 1.9 +/- 0.7% and 131I-HDA 1.6 +/- 0.6%. Moreover, regional distribution of both iodinated fatty acids was quite comparable with the distribution of 201Tl. We conclude that 131I-HDA and 125I-PPA show similar uptake as 201Tl and are distributed according to coronary artery perfusion, which underscores their value as myocardial imaging agents.

Animals

Influence of propranolol on uptake of radioiodinated heptadecanoic acid and thallium-201 in the dog heart.

In an experimental study, the influence of propranolol on myocardial uptake of radioiodinated heptadecanoic acid (131I-HDA) and thallium-201 (201Tl) in the dog heart was assessed. Uptake of 131I-HDA and 201Tl was evaluated in ten control dogs and in ten dogs 20 min after IV administration of propranolol (0.15 mg/kg). In both groups, four healthy dogs were studied and six dogs were studied after coronary artery occlusion. It was shown that both total uptake of 131I-HDA and 201Tl did not alter significantly, regardless of significant changes in hemodynamic parameters and total arterial plasma FFA levels. However, distribution of both 131I-HDA and 201Tl was markedly affected by propranolol, since the endocardial to epicardial ratio showed significantly higher values in the ischemic myocardial regions. The results of our study indicate that propranolol (1) preserves myocardial perfusion in the normal and acutely ischemic dog heart, and (2) gives a more favorable distribution in the ischemic myocardial region towards the subendocardial layers.

Animals

Myocardial scintigraphy with 123I-labelled heptadecanoic acid in patients with unstable angina pectoris.

Calculation of metabolic turnover rates with 123I-heptadecanoic acid (123I-HA) can detect regional myocardial ischaemia in patients with coronary artery disease. We have previously demonstrated different turnover rates in patients with stable angina compared with myocardial infarction. Twelve patients with unstable angina have now been studied: 8 patients showed imaging defects in 12 different myocardial regions and in 4 no defects were observed. Turnover rates were derived from time-activity curves and expressed in minutes half-time (t 1/2). All 12 regions with accumulation defects showed increased t 1/2 values (45.4 +/- 4.8 min) compared to normally perfused zones (29.1 +/- 3.6 min). The results suggest that the use of 123I-HA can identify ischaemic areas of myocardium in unstable angina and that the turnover of 123I-HA is different from that already established in the areas with infarction.

Angina Pectoris

Labelled bleomycin as a tumour-localizing agent. II. The effect of dose loading of the different forms of 57Cobalt-bleomycin A2, B2, and pepleomycin on the tissue distribution and tumour uptake in tumour-bearing rats.

The different forms of 57cobalt-bleomycin (57C0-blm) A2 and B2 as well as 57Co-pepleomycin (57Co-pep), were investigated in tumour-localizing properties of both forms of 57Co-blm are identical if 57Co-blm is injected as a bleomycin solution without carrier cobalt. Differences between the biological behaviour of the various cobalt complexes (which differ in ligand arrangement) were found if these complexes were injected together with inactive cobalt bleomycin complexes of the same form. In this case Co-blm B2 form I and Co-pep form I localize better than Co-blm b2 form II and Co-pep form II respectively. Such a decrease in uptake by the tumour, compared with form I, was not observed for Co-blm A2-II.

Absorption

Labeled bleomycin as a tumor localizing agent III. Selectivity of tumor tissue uptake of the different forms of [57Co] bleomycin A2 and B2.

The cell uptake of the different forms (I and II) of [57Co]bleomycin A2 and B2 was studied in a Rhabdomyosarcoma cell culture. The results show that the uptake of form I appears to be significantly higher than the uptake of form II. The evidence presented indicates that form I is formed in vivo as well as in vitro from form II by biotransformation. Transferrin stimulates the uptake of Co-bleomycin B2 form I only. As a result of trypsin treatment, it is suggested that form II binds only on the outer cell membrane and is not able to pass this membrane.

Animals

Different iron(II) complexes of bleomycin A2.

By 13C-nmr on iron-bleomycin preparations, an iron-bleomycin-CO complex is found that loses its CO upon standing, as demonstrated using 14CO. Iron-bleomycin, prepared without rigorous exclusion of oxygen, reacts with CO to a stable diamagnetic iron-bleomycin-CO complex.

Bleomycin

Demethylation and auto-oxidation of different cobalt-=bleomycin complexes.

Demethylation of Co-bleomycin A2 by heating yields three different complexes: form I and form II and "orange" Co-bleomycin-demethyl A2. These complexes can be separated by HPLC and show different 1H NMR spectra. Preparation of Co-bleomycin-demethyl A2 by chelation of bleomycin-demethyl A2 with cobalt yields a Co-bleomycin-demethyl A2, which is auto-oxidized into Co-bleomycin A1.

Bleomycin

A comparison between terminally radioiodinated hexadecenoic acid (125I-HA) and heptadecanoic acid (131I-H0A) in the dog heart.

The regional myocardial distribution of 125I-16-iodo-9-hexadecenoic acid (125I-HA) and 131I-17-iodo-heptadecanoic acid (131I-H0A) was determined in one normal dog and in five dogs within 5 min after coronary artery occlusion. The total myocardial uptake of 125I-H A was about 40% lower than that of 131I-H0A. The ratio 125I:131I in the normally perfused parts of the myocardium was 0.38-0.81, but the ischemic tissue showed a higher 125I:131I ratio (0.87-1.03), due to lower accumulation of 131I-H0A in ischemic myocardium. We conclude that both radioiodinated fatty acids are reliable indicators of myocardial perfusion and that iodo-heptadecanoic acid, when labeled with 123I, may be preferred to iodo-hexadecenoic acid as the labeled fatty acid for cardiac imaging agent in clinical practice.

Animals