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Wim Oyen

Publications and source records attributed to Wim Oyen.

9 recordsLinked to original sources
PubMed2006

Software package for integrated data processing for internal dose assessment in nuclear medicine (SPRIND).

PURPOSE: Internal radiation dose calculations are normally carried out using the Medical Internal Radiation Dose (MIRD) schema. This requires residence times of radiopharmaceutical activity and S-values for all organs of interest. Residence times can be obtained by quantitative nuclear imaging modalities. For dealing with S-values, the freeware packages MIRDOSE and, more recently, OLINDA/EXM are available. However, these software packages do not calculate residence times from image data. METHODS AND RESULTS: For this purpose, we developed an IDL-based software package for integrated data processing for internal dose assessment in nuclear medicine (SPRIND). SPRIND allows reading and viewing of planar whole-body scintigrams. Organ and background regions of interest (ROIs) can be drawn and are automatically mirrored from the anterior to the posterior view. ROI statistics are used to obtain anterior-posterior averaged counts for each organ, corrected for background activity and attenuation. Residence times for each organ are calculated based on effective decay. The total body biological half-time is calculated for use in the voiding bladder model. Red bone marrow absorbed dose can be calculated using bone regions in the scintigrams or by a blood-derived method. Finally, the results are written to a file in MIRDOSE-OLINDA/EXM format. Using scintigrams in DICOM, the complete analysis is gamma camera vendor independent, and can be performed on any computer using an IDL virtual machine. CONCLUSION: SPRIND is an easy-to-use software package for radiation dose assessment studies. It has made these studies less time consuming and less error prone.

Algorithms↗
PubMed2006

Quantification of FDG PET studies using standardised uptake values in multi-centre trials: effects of image reconstruction, resolution and ROI definition parameters.

PURPOSE: Standardised uptake values (SUVs) depend on acquisition, reconstruction and region of interest (ROI) parameters. SUV quantification in multi-centre trials therefore requires standardisation of acquisition and analysis protocols. However, standardisation is difficult owing to the use of different scanners, image reconstruction and data analysis software. In this study we evaluated whether SUVs, obtained at three different institutes, may be directly compared after calibration and correction for inter-institute differences. METHODS: First, an anthropomorphic thorax phantom containing variously sized spheres and activities, simulating tumours, was scanned and processed in each institute to evaluate differences in scanner calibration. Secondly, effects of image reconstruction and ROI method on recovery coefficients were studied. Next, SUVs were derived for tumours in 23 subjects. Of these 23 patients, four and ten were scanned in two institutes on an HR+ PET scanner and nine were scanned in one institute on an ECAT EXACT PET scanner. All phantom and clinical data were reconstructed using iterative reconstruction with various iterations, with both measured (MAC) and segmented attenuation correction (SAC) and at various image resolutions. Activity concentrations (AC) or SUVs were derived using various ROI isocontours. RESULTS: Phantom data revealed differences in SUV quantification of up to 30%. After application-specific calibration, recovery coefficients obtained in each institute were equal to within 15%. Varying the ROI isocontour value resulted in a predictable change in SUV (or AC) for both phantom and clinical data. Variation of image resolution resulted in a predictable change in SUV quantification for large spheres/tumours (>5 cc) only. For smaller tumours (<2 cc), differences of up to 40% were found between high (7 mm) and low (10 mm) resolution images. Similar differences occurred when data were reconstructed with a small number of iterations. Finally, no significant differences between MAC and SAC reconstructed data were observed, except for tumours near the diaphragm. CONCLUSION: Standardisation of acquisition, reconstruction and ROI methods is preferred for SUV quantification in multi-centre trials. Small unavoidable differences in methodology can be accommodated by performing a phantom study to assess inter-institute correction factors.

Algorithms↗
PubMed2006

Commonly used imaging techniques for diagnosis and staging.

Imaging plays a vital role in the management of patients with cancer. Not only is it important for diagnosis, indicating sites of abnormality, and guiding biopsies, but it is also crucial in assessing disease extent and thereby determining treatment. In this review, conventional imaging techniques such as ultrasound, computed tomography, magnetic resonance imaging, and [18F]fluorodeoxyglucose-positron emission tomography are described, with attention to their mechanisms of action, and their strengths and weaknesses in diagnosis and staging of tumors. New developments are addressed and radiation safety issues are highlighted. In addition, we describe current and expected future uses of imaging techniques in oncology. Given that each technique has its inherent strengths and weaknesses, the combination of the methods will result in improved diagnosis, staging, and treatment prediction and monitoring.

Contrast Media↗
PubMed2004

PET radioimmunoscintigraphy of renal cell cancer using 89Zr-labeled cG250 monoclonal antibody in nude rats.

INTRODUCTION: With the introduction of positron-emitting radionuclides with half-lifes in days, such as 89Zr and 124I, radioimmunoscintigraphy (RIS) with positron-emitter-labeled monoclonal antibodies (moAbs) becomes feasible. RIS, using positron emission tomography (immuno-PET), combines the specific localization of an antibody with the high resolution of a PET camera. In the present study, scintigraphic tumor imaging using chimeric moAb G250 labeled with 89Zr (immuno-PET) or 111In (RIS), and [18F]FDG-(PET) was explored in rats with s.c. renal cell carcinoma (RCC) tumors. METHODS: Nude rats (6-8 rats per group) with s.c. SK-RC-52 tumors were i.v. injected with 4 MBq 111InDTPA-cG250, 20 MBq 89Zr-Df-cG250 or 4 MBq [18F]FDG. Planar 111In-DTPA-cG250 images were obtained 5 minutes, and 24, 48, and 72 hours postinjection (p.i.). 3D PET imaging was performed 5 minutes, and 24, 48, and 72 hours after a 89Zr-Df-cG250 injection and 1 hour after a [18F]FDG injection using a Siemens ECAT EXACT PET camera. Rats were killed after the last imaging session, and the uptake of the radiolabel in the dissected tissues was determined. RESULTS: Both radiolabeled antibody preparations were stable during 4 days of incubation in serum at 37 degrees C, and the immunoreactivity was preserved. Two (2) days after injection, s.c. tumors (100 mg) were clearly visualized, both with 89Zr-Df-cG250 and 111In-DTPA-cG250. Tumors were not visualized with [18F]FDG (uptake in tumor of 0.5 +/- 0.1 %ID/g, 1 hour p.i.). The biodistribution experiments showed an identical uptake in the tumor for both 89Zr-Df-cG250 and 111In-DTPA-cG250 at 3 days p.i. (5.0 +/- 2.4 and 4.9 +/- 2.9 %ID/g, respectively). Blood levels at 3 days p.i. were also identical (1.4 +/- 0.4 versus 1.7 +/- 0.7 %ID/g), and no significant differences were found in the biodistribution of normal tissues between the two radiolabeled cG250 preparations. CONCLUSION: The cG250 antibody can be stably labeled with the positron-emitter 89Zr, while preserving the immunoreactivity of the moAb. In this rat model, the in vivo biodistribution of 89Zr-Df-cG250 was identical to that of 111In-DTPA-cG250. Immuno-PET of RCC is feasible with 89Zr-cG250, and relatively small tumors could be visualized, even without a dedicated PET camera for small animals.

Animals↗
PubMed2004

Improved tumor targeting of radiolabeled RGD peptides using rapid dose fractionation.

Arginine-glycine-aspartic acid (RGD) peptides preferentially bind to alphavbeta3 integrin, an integrin expressed on newly formed endothelial cells and on various tumor cells. When labeled with beta-emitting radionuclides, these peptides can be used for peptide-receptor radionuclide therapy of malignant tumors. These studies aimed to investigate whether tumor targeting and tumor therapy could be optimized by dose fractionation. The RGD-peptide DOTA-E-[c(RGDfK)]2 was labeled with 111In for biodistribution experiments and with 90Y for therapy experiments. In mice with NIH:OVCAR-3 ovarian carcinoma xenografts, optimal tumor uptake was obtained at peptide doses up to 1.0 microg (4.8 %ID/g). A peptide dose of 5 microg, required to administer the maximum tolerable dose (MTD) 90Y-DOTA-E-[c(RGDfK)]2, was administered as 5 portions of 1.0 microg. Tumor uptake of the fifth portion was significantly higher than that of the single 5.0 microg portion (3.3 %ID/g versus 2.1 %ID/g). The therapeutic efficacy of 37 MBq 90Y-DOTA-E-[c(RGDfK)]2 (1 x 5.0 microg) was compared with that of 37 MBq administered in five equal portions (5 x 1.0 microg). No difference in tumor growth between the fractionated and the nonfractionated therapy was observed. In conclusion, dose fractionation resulted in higher radiation doses. However, therapeutic efficacy of the radiolabeled peptide was not significantly improved by dose fractionation.

Animals↗
PubMed2004

Tracers to monitor the response to chemotherapy: in vitro screening of four radiopharmaceuticals.

OBJECTIVES: It has been postulated that radiopharmaceuticals can be used to predict the therapeutic response to (chemo)therapy, which could lead to individualized treatment regimens. In this study, 18F-deoxyglucose, 99mTc-tetrofosmin, 125I-deoxyuridineribose, and 125I-methyltyrosine were tested for this purpose. METHODS: The uterine sarcoma cell line MES-SA (MDR-) and its multidrug resistant variant, MES-SA/Dx5 (MDR+), were used. The MDR+ cells express high levels of P-glycoprotein, which makes them relatively resistant to various chemotherapeutic agents. Cells were cultured in the presence of escalating concentrations of doxorubicin, and the cellular uptake of the radiopharmaceuticals was determined. RESULTS: Decreasing 18F-deoxyglucose uptake at escalating doxorubicin concentrations reflected the chemosensitivity of the cells: 18F-deoxyglucose uptake in the MDR- cells was reduced to 40% of the baseline level in the presence of 1 microM of doxorubicin, compared to 74% in the MDR+ cells. The 125I-deoxyuridineribose uptake in MDR- cells was reduced to 2% of the baseline level when cultured at a concentration of 1 microM of doxorubicin, while this was 79% in the MDR+ cells. The same trend was observed with 125I-methyltyrosine. The enhanced doxorubicin chemosensitivity of MDR+ cells in the presence of verapamil, a modulator of P-glycoprotein, was reflected by the reduced uptake of 18F-deoxyglucose, 125I-deoxyuridineribose, and 125I-methyltyrosine. Furthermore, baseline 99mTc-tetrofosmin uptake in MDR+ cells was more than six-fold lower than in MDR- cells. CONCLUSION: In the presence of doxorubicin, the uptake of 18F-deoxyglucose, 125I-deoxyuridineribose and, to a lesser extent, 125I-methyltyrosine is more pronouncedly reduced in MDR- cells than in MDR+ cells. The reversal of doxorubicin-resistance of MDR+ cells by verapamil was also reflected by the uptake of 18F-deoxyglucose, 125I-deoxyuridineribose, and 125I-methyltyrosine. 99mTc-tetrofosmin uptake reflected P-glycoprotein expression without exposure to doxorubicin.

DNA↗
PubMed2004

Pharmacokinetics and tumor targeting of 131I-labeled F(ab')2 fragments of the chimeric monoclonal antibody G250: preclinical and clinical pilot studies.

INTRODUCTION: Clinical and animal studies of chimeric monoclonal antibody G250 (moAb cG250) for the targeting of clear-cell renal cell carcinoma (RCC), to date, have been with the intact IgG form. To determine whether F(ab')2 fragments are more suited for radioimmunotherapy (RIT) than intact IgG, biodistribution experiments in nude mice were performed, and a pilot study in RCC patients was carried out. In these studies, the biodistribution, pharmacokinetics, and tumor-targeting characteristics of 131I-cG250-F(ab')2 fragments were determined. METHODS: The biodistribution of intact IgG and F(ab')2 fragments (moAb cG250) was directly compared in mice with subcutaneous (s.c.) RCC xenografts that were coinjected with 125I-cG250-IgG and 131I-cG250-F(ab')2 fragments. Groups of 5 mice were dissected at 1, 2, 3, 5, and 7 days postinjection (p.i.). The activity in tumor and normal tissues was expressed as the percentage of the injected dose per gram (%ID/g). Five (5) patients with evidence of primary RCC on computed tomography (CT) and scheduled for nephrectomy received a diagnostic infusion of 150 MBq 131I-cG250-F(ab')2. At various time points after injection of the antibody preparation (5 minutes, 3 hours, and 1, 2, 3, and 4 days), whole-body gamma camera images were acquired. After surgery, histology was determined and immunohistochemistry was performed. The scintigraphic images were analyzed visually and quantitatively. Radioactivity in whole-body, normal tissues and primary RCC was calculated and expressed as %ID. RESULTS: In mice, 131I-cG250-F(ab')2 fragments cleared faster from the blood and other tissues, and absolute uptake in tumor (3.4 +/- 0.9 %ID/g at 24 hours p.i.) and normal tissues was considerably lower compared to intact 125I-cG250. However, the tissue-to-blood ratios for both antibody preparations were similar for most tissues and at most time points. The results in patients corresponded with the results of the studies in mice. The 131I-cG250-F(ab')2 fragments cleared rapidly from the blood and body. The half-life of the distribution and elimination phase (t(1/2)alpha and t(1/2)beta) in blood of RCC patients were 4.8 +/- 0.9 hours and 29.0 +/- 3.3 hours, respectively. At 4 days p.i., whole-body activity was 20%ID. Faint visualization of tumor was observed in only 2 of 5 patients. CONCLUSIONS: In mice, the tissue-to-blood ratios were similar for intact IgG and the 131I-cG250-F(ab')2 fragments for most tissues and at most time points, although absolute uptake in all tissues was considerably lower for the F(ab')2 fragments. In patients with primary RCC, tumorous kidney tissue was faintly visualized with 131I-cG250-F(ab')2 fragments. The intact IgG form of cG250 appears to be more suitable than cG250-F(ab')2 fragments for targeting clear-cell RCC.

Adult↗
PubMed2003

Nuclear medicine imaging to predict response to radiotherapy: a review.

PURPOSE: To review available literature on positron emission tomography (PET) and single photon emission computerized tomography (SPECT) for the measurement of tumor metabolism, hypoxia, growth factor receptor expression, and apoptosis as predictors of response to radiotherapy. METHODS AND MATERIALS: Medical literature databases (Pubmed, Medline) were screened for available literature and critically analyzed as to their scientific relevance. RESULTS: Studies on 18F-fluorodeoxyglucose PET as a predictor of response to radiotherapy in head-and-neck carcinoma are promising but need confirmation in larger series. 18F-fluorothymine is stable in human plasma, and preliminary clinical data obtained with this marker of tumor cell proliferation are promising. For imaging tumor hypoxia, novel, more widely available radiopharmaceuticals with faster pharmacokinetics are mandatory. Imaging of ongoing apoptosis and growth factor expression is at a very early stage, but results obtained in other domains with radiolabeled peptides appear promising. Finally, for most of the tracers discussed, validation against a gold standard is needed. CONCLUSION: Optimization of the pharmacokinetics of relevant radiopharmaceuticals as well as validation against gold-standard tests in large patient series are mandatory if PET and SPECT are to be implemented in routine clinical practice for the purpose of predicting response to radiotherapy.

Apoptosis↗