Biomedical subjects

G Westera

Publications and source records attributed to G Westera.

At least 19 recordsLinked to original sources

PubMed1997

[123I-alpha-methyltyrosine scintigraphy in malignant melanoma].

AIM: The aim of the study was to evaluate the ranking of the scintigraphy with L-3-123I-alpha-methyltyrosine (123I-AMT) in metastasized melanoma. METHODS: 26 metastases and one primary tumor of a malignant melanoma in six patients were examined with 123I-AMT whole-body scintigraphy and SPECT. Positron Emission Tomography with 2-18F-fluoro-2-desoxy-D-glucose (18F-FDG) was used as the golden standard. RESULTS: With 123I-AMT-SPECT 8/10 metastases in the thorax > 1.6 cm were detected (ratio T/NT 1.2-1.8), metastases < 1.6 cm were not detectable with SPECT. In 123I-AMT whole-body scintigraphy not one lesion showed a positive tumor uptake. CONCLUSION: In single cases 123I-AMT scintigraphy can be helpful in staging of malignant melanoma.

Adult↗

PubMed1997

Radioiodine-labelled alpha-methyl-tyrosine in malignant melanoma: cell culture studies and results in patients.

Tyrosine is a precursor of melanin synthesis and might thus present a valuable marker for melanoma. The aim of this study was to evaluate the uptake of alpha-methyl-tyrosine (AMT) in melanoma cell cultures and to assess its usefulness as a radiopharmaceutical for staging melanoma patients with whole-body scintigraphy. Melanoma (M19-cell lines) and fibroblast (negative control) cell cultures were incubated with 125I-AMT and the radioactive uptake in the cell lines was measured in a gamma-counter over 24 h. For in vivo studies, planar whole-body scintigraphy and single photon emission computed tomography (SPECT) of the tumour region was performed following injection of 250-350 MBq 123I-AMT in six patients with known melanoma metastases. Findings were compared with results of whole-body positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) as a standard of reference. Fibroblasts showed an unchanged uptake of (mean +/- SD) 0.56 +/- 0.09% 15 min and 0.066 +/- 0.09% 24 h, respectively, after incubation of 125I-AMT, whereas there was an increased uptake in melanoma cell cultures over time from 0.9 +/- 0.05% to 7.5 +/- 1.6%. In staging melanoma patients, the sensitivity of whole-body AMT-scintigraphy compared with FDG-PET was 37% (10 of 27 metastases). AMT is transported and metabolized to a high extent in melanoma cells and 123I-AMT is accumulated in melanoma metastases. Owing to its low sensitivity, however, the clinical use of whole-body AMT scintigraphy cannot be recommended.

Adult↗

PubMed1996

Carbon-11 and iodine-123 labelled iomazenil: a direct PET-SPET compari son.

The benzodiazepine receptor ligand iomazenil was labelled with carbon-11 to allow a direct positron emission tomography/single-photon emission tomography (PET/SPET) comparison with the well-known iodine-123 labelled compound. Imaging showed the same regional distribution for both modalities. Blood sample activity was corrected for metabolites by extraction with chloroform and high-performance liquid chromatographic analysis. Metabolism is very fast: 5min after application more than 85% of the plasma activity is present as hydrophilic metabolites. Kinetic methods were used to obtain regional estimates of transport rate constants and receptor concentrations. A three-compartment model was employed which gave transport rate constants for brain uptake (K1) and the distribution volume for the specifically receptor bound compartment (DVS). K1 varied from 0.32 to 0.50ml/min per gram for the cortical regions, cerebellum, thalamus and striatum for PET and SPET. Mean DVS-PET and DVS-SPET values were, respectively, 23+/-5 and 31+/-5ml/g for the occipital cortex, 11+/-3 and 15+/-2ml/g for the cerebellum, 7+/-2 and 11+/-3ml/g for the thalamus, 5+/-3 and 10+/-3ml/g for the striatum, and 3+/-2 and 3+/-1ml/g for the pons. These values correlated very well individually. The coefficient of variation of the SPET parameters was quite comparable to that of the PET parameters, especially after 180min (PET 90min) study duration. Thus quantitative benzodiazepine receptor information can be obtained from dynamic SPET imaging in the same way as with PET.

Adult↗

PubMed1996

Lack of expression of dopamine D2 receptors in malignant melanoma: evidence for interaction of iodobenzofurans with melanin.

OBJECTIVES: (1) To compare scintigraphy using the new dopamine D2 receptor binding radioligand iodobenzofuran (IBF) versus whole-body positron emission tomography (PET) in demonstrating metastasizing melanoma, and (2) to determine, for the first time using a panel of histochemical techniques, whether the ability of D2 receptor binding radioligands to detect melanoma metastases is due to tumor-expressed D2 receptors. METHODS: Seven patients with metastatic melanoma were examined using 123I-IBF scintigraphy. Findings were compared to the results of PET and metastasis histochemistry: D2 receptor mRNA assay (metastases: n = 5; melanoma cell lines: n = 4) using the reverse transcriptase polymerase chain reaction (RT-PCR) versus D2 receptor-transfected Chinese hamster ovary cell controls: in vitro 125I-IBF binding (n = 19), and immunohistochemical staining for dopamine D2 receptor protein (n = 19). RESULTS: IBF scintigraphy detected 2/10 melanoma metastases detected by PET (sensitivity 20%). No dopamine D2 receptor mRNA was found in melanoma cells using RT-PCR. The binding of 125I-IBF correlated with the amount of melanin present in the metastases; two amelanotic melanomas both failed to bind 125I-IBF. Immunohistochemical staining was negative in all metastases. CONCLUSION: Melanoma cells do not appear to express dopamine D2 receptors. Although IBF had high dopamine D2 receptor affinity, its ability to detect melanoma metastases is more likely explained by low affinity binding to melanin than by the presence of dopamine receptors.

Adult↗

PubMed1996

Modeling alternatives for cerebral carbon-11-iomazenil kinetics.

UNLABELLED: The in vivo binding kinetics of [11C]iomazenil, a central benzodiazepine antagonist, were analyzed using PET and compartmental modeling. This method is of interest because it allows validation of the SPECT tracer [123I]iomazenil. METHODS: The experimental protocol consisted of serial PET imaging following a single bolus injection of the serial PET imaging following a single bolus injection of the radioligand. Imaging was performed on five healthy young volunteers over 106 min. The tissue time-activity curves of various brain regions were analyzed with models consisting of two (K1, k2") and three (K1, k2', k3', k4) compartments. Some of the methods use simultaneous fitting of the data from multiple brain regions coupled with common parameters. Distribution volumes and k3-based parameters [(K1/k2') k3' and k3')] were chosen to represent receptor density. Goodness of fit was assessed with F-test statistics and chi-square analysis. RESULTS: Compared with the two-compartment model, goodness of fit was significantly improved by all three-compartment configurations. Of the three-compartment models, goodness of fit was similar for the configurations with K1/k2', k4 or no parameter coupled, and slightly worse when both parameters were coupled. The most reliable estimates of receptor density were obtained from the specific distribution volumes (DVs) calculated with the three-compartment model, and the coupling of k4 or both k4 and K1/k2'. Due to oversimplification of the kinetics, the DV values calculated with the two-compartment model were underestimated. CONCLUSION: Reliable quantitative information regarding benzodiazepine receptor density following bolus injection of iomazenil is best obtained by tracer kinetic modeling that uses a three-compartment model and parameter coupling.

Adult↗

PubMed1995

[Dopamine-D2 receptor scintigraphy with 123I-iodobenzofuran in malignant melanoma].

In recent publications dopamine-D2 receptor scintigraphy with benzamides was postulated for specific imaging of melanoma. In a prospective study the value of 123I-iodobenzofuran (IBF), a highly specific and affine dopamine-D2 receptor ligand was evaluated for the detection of melanoma metastases. With IBF-D2 receptor scintigraphy only 2 of 17 melanoma metastases could be detected. The interpretation of the abdomen was impaired by the hepatobiliary and renal excretion of the radionuclide. The ratio striatum/frontal cortex of 2.75 +/- 0.49 3 h p.i. demonstrated a high D2-receptor binding of the ligand. IBF-D2-receptor scintigraphy is not suitable as a method of staging melanoma.

Adult↗

PubMed1995

Iodine-123-IBF SPECT evaluation of extrapyramidal diseases.

UNLABELLED: Iodine-123-IBF is a dopaminergic antagonist suitable for SPECT imaging of D2 receptors. Initial animal studies demonstrated that its affinity for D2 receptors is approximately four times that of the commonly used SPECT D2 ligand [123I]IBZM. In this study we investigated whether this higher affinity would lead to an improved accuracy in differentiating between various extrapyramidal diseases. METHODS: SPECT imaging was performed in 17 patients with idiopathic Parkinson's syndrome (IPS); 4 patients with progressive supranuclear palsy (PSP), 2 patients with multiple system atrophy (MSA) and 7 age-matched control subjects. SPECT imaging was performed 5, 60, 120 and 180 min following intravenous bolus injection of 150-250 MBq of [123I]IBF. The ratio of ligand uptake in the basal ganglia and frontal cortex was determined as a measure of receptor status. RESULTS: In PSP and MSA patients, the basal ganglia-to-frontal cortex ratio reached a plateau at 2 hr; in the control subjects and the IPS patients the ratio was steadily increasing. At 3 hr the basal ganglia-to-frontal cortex ratio was 2.66 +/- 0.29 (control subjects), 3.01 +/- 0.41 (IPS), 2.09 +/- 0.22 (PSP) and 2.10 (MSA). In the IPS patients with predominantly one-sided symptoms, the striatum contralateral to symptoms showed a tendency towards relatively increased ligand uptake. Despite the higher affinity of IBF for the D2 receptor compared to IBZM, the separation of individual PSP and MSA patients from the control subjects was not as clear cut as reported for IBZM due to a relatively high variation in the control subjects. We hypothesize that the latter is due to imaging in nonequilibrium conditions. CONCLUSION: The data suggest that IBF-SPECT can help in discriminating extrapyramidal disease. The accuracy might be improved by an administration protocol that allows imaging in "true equilibrium" conditions, such as a bolus injection followed by a constant infusion.

Aged↗

PubMed1994

Differences in biodistribution of the anti-(carcinoembryonic antigen) murine monoclonal antibody CE-25, its F(ab')2 fragment and its intact mainly human chimeric form CE 4-8-13. Dependence on tumour size and amount of antibody injected.

The effect of the size of the tumour and the amount of antibody injected on the biodistribution of a family of radioiodinated antibodies was studied. The intact mouse anti-(carcinoembryonic antigen) (anti-CEA) monoclonal antibody CE-25, its F(ab')2 fragment and the intact human-mouse chimeric from CE 4-8-13 were evaluated in a model system using the human CEA-producing colon xenograft T 380 grown in nude mice. The relative retention (the percentage of the injected dose per gram of tissue), of mouse mAb and F(ab')2 in tumour and most normal tissues 1 day after injection was independent of the antibody dose; after 4 days the mAb values increased with increasing antibody dose. The relative retention of chimeric mAb increased with increasing antibody dose 1 day after injection and also slightly after 4 days. The relative retention in tumour tissue was lower in bigger xenografts for all antibodies. The relative retention of mouse mAb in small tumours increased from day 1 to day 4; for chimeric mAb this value decreased. In normal tissues the relative retention of mouse mAb decreased from day 1 to day 4, but the relative retention of chimeric mAb in normal tissue dropped rapidly and changed little afterwards. Thus the biokinetics of antibodies is "species"-dependent: foreign, mainly human, chimeric antibody clears faster from normal mouse tissue than mouse antibody and reaches lower concentrations.

Animals↗

PubMed1993

[Positron-emission tomography (PET)--basic considerations].

A PET installation is a technically complex system composed essentially of two parts. The first consists in isotope production and synthesis of labeled biochemical compounds, the second in measuring the distribution of radioactivity in the body with the PET camera and the generation of image data. The specific advantage of PET lies on one hand in the use of positron emitters that are isotopes of ubiquitous elements in biologic matter, i.e. exact analogs of biomolecules can be produced and utilized and on the other hand quantification is possible. (= enable quantitative...?) Theoretically there are no limits for the synthesis of radioactive compounds and the method therefore provides unlimited test designs. The short half-life of the employed isotopes is advantageous for radioprotection reasons but the production of labeled compounds necessitates a cyclotron accelerator and a special laboratory for the handling of radioactive compounds rendering the production of the test substances relatively expensive. Measurements take place in a PET camera with a large number of coincidence detectors. The best available cameras have a spatial resolution of 5 mm in all three axes with an axial window of about 15 cm diameter. Evaluation of PET images is done in a qualitative way by superposition on anatomic images (CT, MRI) by image fusion. Quantitative determinations require elaborate computer modeling.

Cyclotrons↗

PubMed1991

Analysis of time-activity curves related to myocardial metabolism. The case of 123I-heptadecanoic acid.

Time-activity curves are frequently used in the external assessment of the kinetics of radiolabelled non-esterified fatty acids. Analysis of time-activity curves is accomplished by fitting an analytical curve through the data points of the time-activity curve, resulting in two or more parameters of the curve fit. Before interpreting the results of curve fitting, the precision of each of the parameters has to be determined. In the present study the precision of the parameters of monoexponential plus constant curve fit of time-activity curves after administration of 123I-heptadecanoic acid was assessed for an acquisition time of 75 min. Two parameters were used, the T1/2 of the monoexponential and the ratio A/A+C, where A is the amplitude of the monoexponential and C the constant. A model study was used to assess the precision of the parameters of curve fitting. The precision of the parameters was calculated for wide ranges of the T1/2 (0-60 min), A/A+C (0-100%) and the noise content of the time-activity curve. The results are presented as the 10th and 90th percentiles.

Animals↗

PubMed1991

Radioimmuno positron emission tomography with monoclonal antibodies: a new approach to quantifying in vivo tumour concentration and biodistribution for radioimmunotherapy.

Radioimmunodetection of tumours with monoclonal antibodies is becoming an established procedure. Positron emission tomography (PET) shows better resolution than normal gamma camera single photon emission tomography and can provide more precise quantitative data. Thus, in the present study, these powerful methods have been combined to perform radioimmuno PET (RI-PET). Monoclonal antibodies directed against carcinoembryonic antigen (CEA) an IgG, its F(ab')2 and a mouse-human chimeric IgG derived from it were labelled with 124I, a positron-emitting radionuclide with a convenient physical half-life of four days. Mice, xenografted with a CEA-producing human colon carcinoma, were injected with the 124I-MAb and the tumours were visualized using PET. The concentrations of 124I in tumour and normal tissue were determined by both PET and direct radioactivity counting of the dissected animals, with very good agreement. To allow PET quantification, a procedure was established to account for the presence of radioactivity during the absorption correction measurement (transmission scan). Comparison of PET and tissue counting indicates that this novel combination of radioimmunolocalization and PET (RI-PET) will provide, in addition to more precise diagnosis, more accurate radiation dosimetry for radioimmunotherapy.

Animals↗

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↗