Biomedical subjects

G Westera

Publications and source records attributed to G Westera.

At least 37 records · Page 2Linked to original sources

PubMed1990

Imaging and therapy of small cell carcinoma xenografts using 131I-labeled monoclonal antibody SWA11.

The IgG2a monoclonal antibody SWA11 has been evaluated as a radioimmunotherapeutic agent for use in the treatment of small cell cancer of the lung. This antibody was initially selected for in vivo localization studies in a nude mouse model system because of its high affinity for the SW2 small cell cancer cell line in vitro. Following i.v. injection of 125I labeled antibody into nude mice bearing SW2 xenografts good selective accumulation was observed with 10.5% of injected material/g of tumor. The level remained constant from day 2 to day 4 following injection. At day 4 the tumor:blood ratio was 7:1 and tumor:liver, tumor:kidney, and tumor:lung ratios were 17:1, 24:1, and 12:1, respectively. Initial radioimmunotherapeutic studies performed on established small cell cancer of the lung xenografts have shown reduction in tumor burden following a single injection of 300 microCi of 131I labeled SWA11 with no evidence of regrowth up to day 34 postinjection. Histological evaluation of treated tumors revealed large areas of necrosis and extensive fibrosis. A few residual cells of tumor origin could be observed and these displayed atypical morphology. The clonogenic potential of such cells remains to be determined by long term observation.

Animals↗

PubMed1990

The influence of lactate and dipyridamole on myocardial fatty acid metabolism in man, traced with 123I-17-iodoheptadecanoic acid.

Changes in myocardial metabolism can be detected externally by registration of time-activity curves after administration of radioiodinated fatty acids. In this scintigraphic study the influence of lactate on fatty acid metabolism was investigated in the normal human myocardium, traced with 123I-17-iodoheptadecanoic acid (123I-17-HDA). In patients (paired, n = 7) lactate loading decreased the uptake of 123I-17-HDA significantly from 27 (control: 22-36) to 20 counts/min/pixel (16-31; p less than 0.05 Wilcoxon). The half-time value increased to more than 60 min (n = 5), oxidation decreased from 61 to 42%. Coronary vasodilatation, a well-known side effect of lactate loading, was studied separately in a dipyridamole study (paired, n = 6). Coronary vasodilatation did not influence the parameters of the time-activity curve. These results suggest that changes in plasma lactate level as occurring, among other effects, during exercise will influence the parameters of dynamic 123I-17-HDA scintigraphy of the heart.

Aged↗

PubMed1989

Immunolocalisation and imaging of small cell cancer xenografts by the IgG2a monoclonal antibody SWA11.

We describe here a murine monoclonal antibody of the IgG2a isotype which was generated against the SW2 human small cell carcinoma cell line. The antibody, SWA11, was shown to bind to a partially defined antigen preferentially expressed on cell lines of small cell carcinoma origin. In vitro binding studies revealed 6.1 x 10(5) antigenic sites on the SW2 cell line and the Ka to be 1.2 x 10(9)M-1. Following injection into mice bearing 1-2 cm3 SW2 xenografts, SWA11 showed strong selective accumulation in the small cell heterotransplants with a tumour to blood ratio of 7.5:1 at day 4. Other tumour to organ ratios were similarly high at 19:1, 22:1 and 12:1 for liver, kidney and spleen respectively. The absolute amount of SWA11 which localised was 10.5% of total injected material per gram tumour at day 2 and this level did not markedly decrease by day 4. The high ability of SWA11 to localise to SCC xenografts was confirmed by external gamma scintigraphy. The potential application of SWA11 as a model system for in vivo radioimmunotherapy is discussed.

Animals↗

PubMed1987

Analysis of myocardial time-activity curves of 123I-heptadecanoic acid. I. Curve fitting.

Myocardial time-activity curves can be described by two or more parameters. To establish the optimal curve fitting method 33 myocardial time-activity curves were analyzed with different curve fitting methods: monoexponential, biexponential and monoexponential plus constant. A background correction was not applied. Biexponential curve fitting resulted in redundancy of parameters. Optimal curve fitting was obtained with monoexponential plus constant. The constant represents the background activity together with the stored radiolabelled lipids and the half-time value represents the wash-out of radioiodide from the myocardium. A strong relation was found between the constant and the half-time value: small errors in the determination of the constant (background activity) resulted in considerable errors of the half-time value. It is concluded that optimal analysis of a myocardial time-activity curve can be performed with a monoexponential plus constant without earlier correction for background activity.

Coronary Disease↗

PubMed1987

Analysis of myocardial time-activity curves of 123I-heptadecanoic acid. II. The acquisition time.

Optimal fitting of a myocardial time-activity curve is accomplished with a monoexponential plus a constant, resulting in three parameters: amplitude and half-time of the monoexponential and the constant. The aim of this study was to estimate the precision of the calculated parameters. The variability of the parameter values as a function of the acquisition time was studied in 11 patients with cardiac complaints. Of the three parameters the half-time value varied most strongly with the acquisition time. An acquisition time of 80 min was needed to keep the standard deviation of the half-time value within +/- 10%. To estimate the standard deviation of the half-time value as a function of the parameter values, of the noise content of the time-activity curve and of the acquisition time, a model experiment was used. In most cases the SD decreased by 50% if the acquisition time was increased from 60 to 90 min. A low amplitude/constant ratio and a high half-time value result in a high SD of the half-time value. Tables are presented to estimate the SD in a particular case.

Coronary Disease↗

PubMed1986

Uptake of a monoclonal antibody against CEA (Tumak 431/31) in a human colon tumor (Co-112) xenografted in the nude mouse. Dependence on tumor size and injected dose.

A monoclonal antibody (Tumak) against carcinoembryonic antigen (CEA) was injected into nude mice bearing a human colon carcinoma (Co-112). The tumor uptake was found to be dependent on the size of the tumors: relative uptake (percentage of the injected dose/gram tumor (% i.d./g) decreased for tumors with weights up to approximately 1 g, although the absolute uptake (% i.d./tumor) still increased over the same weight range. In the constant region (greater than or equal to 1 g) mean relative tumor uptake was approximately 4% i.d./g. The same tumor size dependence was found for the relative Tumak uptake in the other mouse organs studied (e.g., blood, liver, spleen and muscle). Consequently tumor/organ ratios were found to be independent of tumor size. Tumor uptake was also studied for various doses of Tumak (0.07-120 micrograms) in tumors of approximately 1 g. Evidence was found for a threshold dose of 0.1 microgram under which no serious tumor uptake appeared. From 1 to 120 micrograms no further dependence of Tumak distribution on applied dose was found: the relative uptake of all organs remained the same but the absolute uptake increased with dose.

Animals↗

PubMed1985

The myocardial elimination rate of radioiodinated heptadecanoic acid.

To clarify the mechanism of the elimination of radioactivity after administration of radioiodinated heptadecanoic acid, dogs with and without coronary occlusion were studied. In myocardial tissue samples of normal and ischemic myocardium, the proportions of free radioiodide, radioiodinated heptadecanoic acid, and radioiodinated lipids were determined. Five minutes after intravenous injection of heptadecanoic acid 69% of the radioactivity was present as free iodine, 7% as unaltered heptadecanoic acid, and 24% as lipids. Even in ischemic myocardium 41% was free iodine and 47% lipids. After 2 h free iodine decreased to 48% and lipids increased to 44%. These results indicate that beta-oxidation is not the rate-limiting step in the elimination rate of heptadecanoic acid.

Animals↗

PubMed1985

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↗

PubMed1985

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↗

PubMed1985

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↗

PubMed1985

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↗

PubMed1985

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↗

PubMed1985

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↗

PubMed1984

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↗

PubMed1984

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↗

PubMed1984

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↗

PubMed1984

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↗

PubMed1983

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↗