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  • 1
    Electronic Resource
    Electronic Resource
    Combination treatment based on metabolic effects of dinaline (1995)
    Springer
    Journal of cancer research and clinical oncology 121 (1995), S. 203-210 
    Details
    ISSN: 1432-1335
    Keywords: Dinaline ; 2-Deoxyglucose ; 2-Fluoro-2-deoxy-d-glucose ; Combination treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The human colon carcinoma cell line SW 707 was exposed for up to 72 h to the new antineoplastic agent 4-amino-N-(2′-aminophenyl)benzamide (GOE 1734, dinaline). Thereafter, uptake measurements with fluorodeoxy-[14C]glucose (FdGlc) were performed and cell-cycle fractions as well as adenine nucleotide pools were determined by flow cytometry and HPLC. One day after a 24 h exposure to 20–540 μM dinaline a 2.0-to 2.5-fold enhancement of FdGlc uptake was observed, and the values after 48-h or 72-h incubations showed a 2.5- to 3.5-fold or a 2.0-fold increase respectively. For all periods of exposure a diminished S phase (3%–71% of control) was found initially after incubation, demonstrating the antiproliferative effect of dinaline, with total recovery after 1 day. Adenine nucleotide pools were not diminished concomitantly. The enhanced FdGlc uptake caused by dinaline was the basis for choosing 2-deoxyglucose (dGlc) as the combination partner, which acts as an antimetabolite to enzymes involved in glucose metabolism. Several combinations of dinaline and dGlc were analyzed for their effects on growth inhibition. Almost 50% additional decrease in cell number as compared to monotherapy with dinaline was found after coexposure to 12 mM dGlc and 20 μM dinaline 24 h after incubation. Similar effects were observed 2 days after incubation with the two drugs. After 3 days, the cell numbers reached monotherapy levels. Since the cytostatic effect of dinaline could be enhanced by dGlc although incubation with dGlc alone caused no changes in cell number, the combined effect of both agents is synergistic. These results imply that dinaline might have applications in combination treatment in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01366963
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Measurement of liver blood flow using oxygen-15 labelled water and dynamic positron emission tomography: Limitations of model description (1996)
    Springer
    European journal of nuclear medicine 23 (1996), S. 169-177 
    Details
    ISSN: 1619-7089
    Keywords: Positron emission tomography ; Liver perfusion ; Modelling ; Oxygen-15 labelled water
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To date no satisfactory method has been available for the quantitative in vivo measurement of the complex hepatic blood flow. In this study two modelling approaches are proposed for the analysis of liver blood flow using positron emission tomography (PET). Five experiments were performed on three foxhounds. The anaesthetised dogs were each given an intravenous bolus injection of oxygen-15 labelled water, and their livers were then scanned using PET. Radioactivity in the blood from the aorta and portal vein was measured directly and simultaneously using closed external circuits. Time-activity curves were constructed from sequential PET data. Data analysis was performed by assuming that water behaves as a freely diffusible tracer and adapting the standard one-compartment blood flow model to describe the dual blood supply of the liver. Two particular modelling approaches were investigated: the dual-input model used both directly measured input functions (i.e. using the hepatic artery and the portal vein input, determined from the radioactivity detected in the aorta and portal vein respectively) whereas the single-input model used only the measured arterial curve and predicted the corresponding portal input function. Hepatic arterial flow, portal flow and blood volume were fitted from the PET data in several regions of the liver. The resulting estimates were then compared with reference blood flow measurements, obtained using a standard microsphere technique. The microspheres were injected in a separate experiment on the same dogs immediately prior to PET scanning. Whilst neither the single- nor the dual-input models accurately reproduced the arterial reference flow values, the flow values from the single-input model were closer to the microsphere flow values. The proposed single-input model would be a good approximation for liver blood flow measurements in man. The observed discrepancies between the PET and microsphere flow values may be due to the inherent temporal and spatial heterogeneity of liver blood flow. The results presented suggest that adaptation of the standard one-compartment blood flow model to describe the dual blood supply of the liver is limited and other flow tracers have to be considered for quantitative PET measurements in the liver.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01731841
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Application of α-aminoisobutyric acid,l-methionine, thymidine and 2-fluoro-2-deoxy-d-glucose to monitor effects of chemotherapy in a human colon carcinoma cell line (1996)
    Springer
    European journal of nuclear medicine 23 (1996), S. 55-60 
    Details
    ISSN: 1619-7089
    Keywords: α-Aminoisobutyric acid ; l-Methionine ; Thymidine ; 2-Fluoro-2-deoxy-d-(U-14C)-glucose ; Dinaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Up to 4 h after treatment of human SW 707 colon carcinoma cells with the antineoplastic drug 4-amino-N-(2′-aminophenyl)-benzamide (GOE 1734, dinaline), the effects of tumour cell metabolism and proliferation were examined in vitro. Four tracers which can be labelled with isotopes suitable for positron emission tomography (PET) were used for this purpose:α-aminoisobutyric acid (AIB) and methionine to study changes in amino acid transport and protein synthesis, thymidine to observe changes in tumour proliferation and 2-fluoro-2-deoxy-d-glucose (FDG) to estimate glucose metabolism. Dinaline showed an inhibition of the sodium-dependent and -independent uptake of AIB. The methionine uptake was found to increase shortly after therapy. Thymidine incorporation into DNA was impaired and the FDG uptake showed a maximally 2.2-fold enhancement. Inhibition of AIB uptake suggests changes in amino acid transport, whereas increased uptake of methionine and FDG points to an enhancement of protein synthesis and glycolysis caused by repair mechanisms. The cytostatic and antiproliferative effect of dinaline, observed in cell growth curves, could be demonstrated by the impaired thymidine incorporation into DNA. This study demonstrates that in vitro screening with radiotracers suitable for PET can help to clarify effects of new antineoplastic substances on tumour cell metabolism. These data may be applied to choose the appropriate time schedule for monitoring therapeutic effects on tumour tissue.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01736990
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Use of scanner characteristics in iterative image reconstruction for high-resolution positron emission tomography studies of small animals (1997)
    Springer
    European journal of nuclear medicine 24 (1997), S. 779-786 
    Details
    ISSN: 1619-7089
    Keywords: Key words: Positron emission tomography ; Spatial resolution ; Image restoration ; Animal studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The purpose of this work was to improve of the spatial resolution of a whole-body positron emission tomography (PET) system for experimental studies of small animals by incorporation of scanner characteristics into the process of iterative image reconstruction. The image-forming characteristics of the PET camera were characterized by a spatially variant line-spread function (LSF), which was determined from 49 activated copper-64 line sources positioned over a field of view (FOV) of 21.0 cm. This information was used to model the image degradation process. During the course of iterative image reconstruction, the forward projection of the estimated image was blurred with the LSF at each iteration step before the estimated projections were compared with the measured projections. The imaging characteristics of the high-resolution algorithm were investigated in phantom experiments. Moreover, imaging studies of a rat and two nude mice were performed to evaluate the imaging properties of our approach in vivo. The spatial resolution of the scanner perpendicular to the direction of projection could be approximated by a one-dimensional Gaussian-shaped LSF with a full-width at half-maximum increasing from 6.5 mm at the centre to 6.7 mm at a radial distance of 10.5 cm. The incorporation of this blurring kernel into the iteration formula resulted in a significantly improved spatial resolution of about 3.9 mm over the examined FOV. As demonstrated by the phantom and the animal experiments, the high-resolution algorithm not only led to a better contrast resolution in the reconstructed emission scans but also improved the accuracy for quantitating activity concentrations in small tissue structures without leading to an amplification of image noise or image mottle. The presented data-handling strategy incorporates the image restoration step directly into the process of algebraic image reconstruction and obviates the need for ill-conditioned ”deconvolution” procedures to be performed on the projections or on the reconstructed image. In our experience, the proposed algorithm is of special interest in experimental studies of small animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00879667
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Use of scanner characteristics in iterative image reconstruction for high-resolution positron emission tomography studies of small animals (1997)
    Springer
    European journal of nuclear medicine 24 (1997), S. 779-786 
    Details
    ISSN: 1619-7089
    Keywords: Positron emission tomography ; Spatial resolution ; Image restoration ; Animal studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this work was to improve of the spatial resolution of a whole-body positron emission tomography (PET) system for experimental studies of small animals by incorporation of scanner characteristics into the process of iterative image reconstruction. The image-forming characteristics of the PET camera were characterized by a spatially variant line-spread function (LSF), which was determined from 49 activated copper-64 line sources positioned over a field of view (FOV) of 21.0 cm. This information was used to model the image degradation process. During the course of iterative image reconstruction, the forward projection of the estimated image was blurred with the LSF at each iteration step before the estimated projections were compared with the measured projections. The imaging characteristics of the high-resolution algorithm were investigated in phantom experiments. Moreover, imaging studies of a rat and two nude mice were performed to evaluate the imaging properties of our approach in vivo. The spatial resolution of the scanner perpendicular to the direction of projection could be approximated by a one-dimensional Gaussian-shaped LSF with a full-width at half-maximum increasing from 6.5 mm at the centre to 6.7 mm at a radial distance of 10.5 cm. The incorporation of this blurring kernel into the iteration formula resulted in a significantly improved spatial resolution of about 3.9 mm over the examined FOV As demonstrated by the phantom and the animal experiments, the high-resolution algorithm not only led to a better contrast resolution in the reconstructed emission scans but also improved the accuracy for quantitating activity concentrations in small tissue structures without leading to an amplification of image noise or image mottle. The presented data-handling strategy incorporates the image restoration step directly into the process of algebraic image reconstruction and obviates the need for ill-conditioned ”deconvolution“ procedures to be performed on the projections or on the reconstructed image. In our experience, the proposed algorithm is of special interest in experimental studies of small animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00879667
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
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