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C Van de Wiele

Publications and source records attributed to C Van de Wiele.

At least 19 recordsLinked to original sources

99mTc-HYNIC Annexin-V imaging of tumors and its relationship to response to radiotherapy and/or chemotherapy.

AIM: The aim of this study was to report on the relationship between preradiotherapy and prechemotherapy 99mTc-HYNIC Annexin-V tumor uptake values, reflecting ongoing apoptosis, and outcome to radiotherapy and/or chemotherapy. METHODS: Twenty-three cancer patients underwent staging examinations and a 99mTc-HYNIC Annexin-V scintigraphy and subsequent radiotherapy and/or chemotherapy. Tumor-to-background ratios derived from tomographic 99mTc-HYNIC Annexin-V images were related to treatment outcome as assessed by RECIST criteria. RESULTS: Six patients underwent radiotherapy or radiochemotherapy: 4 exhibited response to treatment, 1 had stable, and 1 progressive disease. Corresponding tumor-to-background ratio's were respectively >or=2.3 (in responders), 1.2 in the patient presenting with stable disease and 1 in the patient presenting with progressive disease. Seventeen patients were treated by chemotherapy alone: 8 were progressive, 1 patient presented with stable disease and 8 responded to treatment. In 1/8 progressive patients a tumor-to-background ratio of 1.4 was found, the others showed no uptake. In the patient presenting with stable disease a ratio of 0.1 was found. In the 8 responders, 7 patients had a tumor-to-background ratio >or=1.3 whereas in 1 patient a ratio of 0.3 was found. Tumor-to-background ratios in responders (complete plus partial) (median 2.5, range: 0.3-4.2) were significantly higher when compared to those obtained in non-responders (stable plus progressive disease) (median 1, range: 0.1-1.4) (P<0.001). CONCLUSION: The findings presented suggest that 99mTc-HYNIC Annexin-V pretreatment uptake may be useful to predict response to chemo- and radiotherapy.

Adult↗

Optimised tracer-dependent dosage cards to obtain weight-independent effective doses.

PURPOSE: The aim of this study was twofold: firstly, to determine whether the European Association of Nuclear Medicine (EANM) dosage card results in weight-independent effective doses or weight-independent count rates; secondly, to determine whether one dosage card is sufficient for 95 different radiopharmaceuticals, and, if not, how many cards we reasonably need to take into account inter-tracer variability. METHODS: Normalisation factors for count rate and effective dose were calculated as a function of body weight, with 70 kg as standard. Calculations were performed, using whole-body absorption fractions and MIRDOSE 3 software, for seven anthropomorphic phantoms and ten radionuclides. An analytic function for both relations was proposed. Normalisation factors for effective dose for 95 radiopharmaceuticals were investigated using cluster analysis. RESULTS: Normalisation factors for count rate and effective dose can be estimated accurately as a function of body weight W by (W/70)a holding only one parameter, called the a value. The a values for 95 radiopharmaceuticals were classified into three clusters (nA=7, nB=76, nC=12). Cluster A contains tracers for renal studies. Cluster B contains all remaining tracers, except iodine-labelled tracers for thyroid studies and 89Sr for therapy, which belong to cluster C. CONCLUSION: Correction factors proposed by the EANM task group mainly correct for effective dose. They are very similar to the factors obtained for cluster A. Using the EANM factors for tracers belonging to clusters B and C results in significantly higher effective doses to children. We suggest using three tracer-dependent dosage cards for which the correction factors have been calculated to obtain weight-independent effective doses.

Adult↗

Registration accuracy of 153Gd transmission images of the brain.

PURPOSE: The aim of the study was to determine the accuracy of non-rigid nine-parameter image registrations based on 153Gd transmission computed tomography (TCT) images as compared with those based on 99mTc-ethyl cysteinate dimer (ECD) images and to assess whether normalised mutual information (NMI) or count difference (CD) should be used. METHODS: TCT and ECD data were acquired in 25 randomly selected patients. Emission images were registered to an ECD template with a CD cost function. The same registration parameters were applied to the transmission images to create a TCT template. All TCT images were registered to the TCT template and the same registration parameters were applied to the ECD images. The procedure was repeated with NMI as cost function. Accuracy of both ECD-based and TCT-based registrations was assessed by comparing the normalisation parameter values and regional activities in the spatially normalised ECD images, using a mixed-model analysis of variance (ANOVA). Scheffe post hoc tests were performed. RESULTS: No significant differences were found between ECD/CD, ECD/NMI and TCT/CD, suggesting that ECD registration can be done with either CD or NMI, and that TCT registration using CD is equally as accurate as ECD registration. The accuracy of TCT registration with NMI was lower, with discrepancies occurring in the frontal inferior region and the cerebellum. The analysis of normalisation parameters indicated that z-scaling is underestimated and yz-rotation overestimated with TCT/NMI registration. CONCLUSION: We conclude that ECD registrations with CD or NMI are as accurate as TCT registrations with CD and that TCT registrations with NMI should be avoided.

Brain↗

Oestrogen-mediated regulation of somatostatin receptor expression in human breast cancer cell lines assessed with 99mTc-depreotide.

Investigating three somatostatin receptor (SSTR)-positive (+) human breast cancer cell lines, Xu et al. found a time- and dose-dependent up- or down-regulation of SSTR2 mRNA expression by 17beta-oestradiol (E(2)) or the anti-oestrogen tamoxifen, respectively, in the two oestrogen receptor-positive (ER+) cell lines but not in the oestrogen receptor-negative (ER-) cell line. This study aimed to confirm the findings of Xu et al. at the protein level by means of western blotting and saturation binding studies using (99m)Tc-depreotide (NeoSpect). The ER+/SSTR+ ZR75-1 and T47D and SSTR+/ER- MDA MB231 breast cancer cell lines were exposed to 1 n M E(2) or a combination of 1 n M E(2) plus 100 n M tamoxifen or ICI 182 780 (Faslodex) for 48 h. Exposed and non-exposed controls were incubated with increasing concentrations of (99m)Tc-depreotide (0.5 n M-15 n M) in the absence and the presence of 20 micro M of octreotide. Scatchard-Rosenthal plots were derived using commercially available software. SSTR subtypes responsible for E(2)-induced changes in (99m)Tc-depreotide binding were identified by means of western blotting. Mean K(d) values for (99m)Tc-depreotide were 13 n M, 7 n M and 4 n M for T47D, ZR75-1 and MDA MB231 cells, respectively. After stimulation with E(2), the ER+ cell line T47D demonstrated a mean increase of 81% ( P<0.05) in (99m)Tc-depreotide binding. Adding the partial agonist tamoxifen and full antagonist ICI 182 780 to E(2) blocked the induced increase in T47D cells, either reducing SSTR expression or restoring it to control levels. ZR75-1 cells stimulated with E(2) showed a mean decrease in (99m)Tc-depreotide binding of 36% as compared to control cells; this difference, however, proved to be not statistically significant. Similarly, B(max) values did not change in ZR75-1 cells exposed to E(2) in combination with an ER antagonist as compared to control cells. Finally, no influence of E(2) on (99m)Tc-depreotide binding was observed in the ER- cell line MDA MB231. Both SSTR2 and SSTR5 were expressed at high levels in T47D cells and ZR75-1 cells. SSTR5 drastically increased in the absence of E(2) and was restored to the original detection level after E(2) treatment. The presented findings support an oestrogen-dependent regulation of SSTR expression in breast cancer cell lines.

Adult↗

Radioimmunoimaging. Advances and prospects.

The advent of biotechnology has made it possible to overcome the undesired host antiglobulin response evidenced following the injection of rodent antibodies for radioimmunoimaging; initially through the construction of chimeric and CDR-grafted antibodies and more recently through the derivation of completely human antibodies. Available platforms for derivation of completely human antibodies include phage- and ribosome-display techniques and transgenic mice that are deleted in their own antibody genes and reconstituted with large parts of the genes encoding for human antibodies. Additionally, biotechnology has made it possible to tailor affinity, respectively through CDR-walking or chain schuffling, and avidity, respectively through manifold engineering, of antibodies and derivatives. More recent developments include the development of highly stable single domain binders based on the use of a conserved framework region and a highly variable antigen-binding site, using other proteins or molecules that are smaller in size and easier to manufacture than antibodies. Finally, novel technologies have been and are being developed optimizing the concept of pretargeting.

Animals↗

Leakage assessment in adjustable laparoscopic gastric banding: radiography versus (99m)Tc-pertechnetate scintigraphy.

The least invasive of all surgical weight-lowering procedures is the adjustable laparoscopic gastric banding (ALGB) technique. A rare complication (0.9%-1.8% of patients) but one that may require surgical revision is leakage of the gastric banding device. This paper reports on the usefulness of technetium-99m scintigraphy for the assessment of gastric band leaks as compared with radiography. Between March 1997 and October 2001, 23 obese patients (20 women and 3 men; mean age 35 years; range 23-60 years; mean body mass index before gastric banding procedure, 39.2 kg/m(2); range 29.3-52.1 kg/m(2)) were referred for exclusion of gastric banding leakage by means of radiography and (99m)Tc-pertechnetate scintigraphy. Both procedures were performed on the same day in all patients. Two patients underwent both procedures, respectively two and three times. A total of 27 radiographic and scintigraphic examinations were performed. Radiographs were judged positive for leakage when escape of contrast agent through a defect in the gastric banding device was visualised or when indirect criteria, e.g. smooth passage of barium suspension through the stoma after injection of contrast agent, were present. Scintigraphic images were judged positive when tracer disappearance out of the banding device and uptake in the thyroid gland as well as enhancement of the gastric mucosa were observed 30 min and/or 3 h post injection. Overall sensitivity, specificity and accuracy for radiography and (99m)Tc scintigraphy were 81.8% vs 81.8%, 75% vs 100% and 77.7% vs 92.6%. Leakage from the reservoir or the connecting tube is a late complication of ALGB. The presented data suggest that (99m)Tc-pertechnetate scintigraphy is more efficient than radiography in determining the presence of such leaks.

Adult↗

Peptide radiopharmaceuticals for diagnosis and therapy.

Radiolabelled peptides are an emerging class of radiopharmaceuticals that share chemical and biological properties. From the chemical point of view they have a poly-amino acid structure varying from 3 to more that 200 amino acids, and they are labelled with different isotopes directly or by a linker. Biologically, they bind to specific cell membrane receptors, thus providing in vivo histopathological information for diagnostic purposes, therapy follow-up or targeted radiotherapy. This paper reviews most of the radiolabelled peptides that have been tested in animals and humans in the fields of oncology, neurology, cardiology, inflammation/infection, atherosclerosis and thrombosis. A new classification is also proposed for peptides targeting tumour cells based on the biological function of target receptors. These tailored radiopharmaceuticals are the basis of the new era of "molecular nuclear medicine".

Arteriosclerosis↗

Biodistribution and dosimetry of 99mTc-ciprofloxacin, a promising agent for the diagnosis of bacterial infection.

This study reports on the biodistribution and dosimetry of technetium-99m ciprofloxacin, a radio-ligand developed for the visualisation of bacterial infection. Whole body scans were performed up to 24 h after intravenous injection of 370 MBq 99mTc-ciprofloxacin in three male and three female volunteers. Blood samples were taken at various times up to 24 h after injection. Urine was also collected up to 24 h after injection, allowing calculation of renal clearance and interpretation of whole body clearance. Time-activity curves were generated for the thyroid, heart, liver and whole body by fitting the organ-specific geometric mean counts, obtained from regions of interest. The MIRD formulation was applied to calculate the absorbed radiation doses for various organs. The images showed rapid, predominantly urinary excretion of 99mTc ciprofloxacin, with low to absent brain, lung and bone marrow uptake and low liver uptake and excretion. Accordingly, imaging conditions are excellent for both the thoracic and the abdominal region, even at early time points (60 min) post injection. In none of the volunteers was the gallbladder visualised. Approximately 60% of the injected activity was recovered in urine by 24 h post injection. The highest absorbed doses were received by the urinary bladder wall, the thyroid, the upper large intestine, the lower large intestine and the uterus. The estimated mean effective dose for the adult subject, taking into account the weight factors of the ICRP60 publication, was 0.0083 mSv/MBq. The amount of 99mTc ciprofloxacin required for adequate planar and tomographic imaging results in an acceptable effective dose to the patient.

Adult↗

Age- and gender-specific differences in left ventricular cardiac function and volumes determined by gated SPET.

The aim of this study was to determine normative volumetric data and ejection fraction values derived from gated myocardial single-photon emission tomography (SPET) using the commercially available software algorithm QGS (quantitative gated SPET). From a prospective database of 876 consecutive patients who were referred for a 2-day stress-rest technetium-99m tetrofosmin (925 MBq) gated SPET study, 102 patients (43 men, 59 women) with a low (<10%) pre-test likelihood of coronary disease were included (mean age 57.6 years). For stress imaging, a bicycle protocol was used in 79 of the patients and a dipyridamole protocol in 23. Left ventricular ejection fraction (LVEF) and end-diastolic and -systolic volumes (EDV and ESV) were calculated by QGS. EDV and ESV were corrected for body surface area, indicated by EDVi and ESVi. To allow comparison with previous reports using other imaging modalities, men and women were divided into three age groups (<45 years, > or =45 years but <65 years and > or =65 years). Men showed significantly higher EDVi and ESVi values throughout and lower LVEF values when compared with women in the subgroup > or =65 years (P<0.05, ANOVA). Significant negative and positive correlations were found between age and EDVi and ESVi values for both women and men and between LVEF and age in women (Pearson P< or =0.01). LVEF values at bicycle stress were significantly higher than at rest (P=0.000, paired t test), which was the result of a significant decrease in ESV (P=0.003), a phenomenon which did not occur following dipyridamole stress (P=0.409). The data presented suggest that LVEF and EDVi and ESVi as assessed by QGS are strongly gender-specific. Although the physiological significance of these results is uncertain and needs further study, these findings demonstrate that the evaluation of cardiac function and volumes of patients by means of QGS should consider age- and gender-matched normative values.

Adult↗

Fibrinogen and C-reactive protein on admission as markers of final infarct size after primary angioplasty for acute myocardial infarction.

BACKGROUND: In acute myocardial infarction (AMI) treated conservatively or with thrombolysis, marked increases of C-reactive protein (CRP) and fibrinogen have been observed. No data are however available concerning a possible relation between CRP and fibrinogen levels on admission and markers of infarct size after obtaining thrombolysis in myocardial infarction (TIMI) flow III by primary angioplasty. METHODS: We studied 34 patients with a first AMI (29 men, mean age 54+/-11 years) who were treated with primary angioplasty (TIMI flow III in all patients, no concomitant treatment with glycoprotein IIb-IIIa antagonists) within 6 h of onset of pain. CRP and fibrinogen levels on admission were determined and related to the following markers of infarct size: peak creatine kinase MB (CKMB) levels, radionuclide left ventricular ejection fraction (LVEF) at discharge and thallium-201 single-photon emission computed tomography (SPECT) infarct size at 1 month. RESULTS: Median CRP levels were 0.4 mg/dl (range 0.09-3 mg/dl), median fibrinogen levels 412 mg/dl (range 198-679 mg/dl), mean CKMB was 178+/-151 U/l, mean LVEF 52+/-8% and mean thallium-201 infarct size 7+/-6%. Although CRP levels were related to fibrinogen levels on admission (r=0.56, P=0.002), only fibrinogen levels were related to markers of infarct size (r=0.58, P=0.001 for CKMB, r=-0.44, P=0.01 for LVEF and r=0.64, P=0.001 for thallium-201 infarct size). No relation was found between CRP or fibrinogen levels on admission and the extent of coronary artery disease or the myocardial area at risk. In multiple regression analysis, the relation between fibrinogen and markers of infarct size was independent of CRP levels and the duration of pain on admission. CONCLUSIONS: These findings indicate a relation between fibrinogen levels on admission and myocardial infarct size in patients treated with primary angioplasty for AMI. This relation seems to be independent of CRP levels and the duration of pain on admission. If confirmed in larger patient populations, fibrinogen levels on admission could have an important value for risk stratification and more aggressive reduction of infarct size in patients who are treated with primary angioplasty.

Acute Disease↗

High performance liquid chromatographic determination of 123-I labeled tamoxifen metabolites in human plasma.

A high-performance liquid chromatographic procedure for the quantitation of [(123)I]Iodomethyl-N,N-diethyltamoxifen (ITX), a radioligand for human breast cancer imaging, in human plasma is described. Separation was effected on a RP-C18 column, using a mixture of acetonitrile-water-triethylamine (70/30/0.5, v/v). ITX was rapidly cleared from human plasma and metabolites appeared as early as 7.5 min p.i. Quantitative assessment of metabolites in plasma over time allowed recalculation of the ITX plasma time-activity curve. Implications of ITX metabolite formation for breast tumour imaging are discussed.

Aged↗

Synthesis and in vitro evaluation of 123I-labelled human recombinant annexin V.

Annexin V was radiolabelled with iodine-123 in order to develop a SPECT-ligand for imaging atherosclerosis and apoptosis. Iodination by means of electrophylic substitution resulted in radiochemical yields up to 70% and specific activities of 7.4-92.5 MBq/microg protein. Binding experiments with blood platelets indicated that 123I-labelled annexin V remained its biological activity.

Annexin A5↗

Is there a role for agonist gastrin-releasing peptide receptor radioligands in tumour imaging?

Gastrin-releasing peptide (GRP) has been shown to be a tumour growth stimulating agent for a number of normal and human cancer cell lines. The tumour growth effect is a direct result of GRP binding to membrane G-protein coupled GRP receptors (GRP-R) on the cell surface. Available data on the role of GRP and GRP-R in human lung, prostate, breast, colorectal and gastric carcinoma are reviewed and it is suggested that radiolabelled agonists are preferable to antagonists for imaging and therapy as they appear to be internalised, yielding a higher target/background ratio. The use of rhenium or indium radiolabels for therapy may provide a new approach to GRP/bombesin expressing tumours.

Bombesin↗

Biodistribution and dosimetry of (99m)Tc-RP527, a gastrin-releasing peptide (GRP) agonist for the visualization of GRP receptor-expressing malignancies.

UNLABELLED: The aim of this study was to determine the human biodistribution and radiation dosimetry of (99m)Tc-RP527, a promising radioligand for the visualization of gastrin-releasing peptide (GRP) receptor-expressing human malignancies. METHODS: Whole-body scans were obtained up to 48 h after intravenous injection of 555 MBq (99m)Tc-RP527 in each of 6 subjects. Blood samples were taken at various times up to 48 h after injection. Urine was collected up to 48 h after injection for calculation of renal clearance and whole-body clearance. Time-activity curves were generated for the thyroid, heart, breasts in women, testes in men, and liver by fitting the organ-specific geometric mean counts, obtained from regions of interest, on the respective images as a function of the time after injection. The MIRD formulation was applied to calculate the absorbed radiation dose for various organs. RESULTS: The serial whole-body images showed rapid hepatobiliary excretion, resulting in low background and potentially high-contrast imaging of the thoracic region. Imaging of abdominal tumors may prove problematic, however, because of the extensive bowel activity. (99m)Tc-RP527 was predominantly cleared by the kidneys and to a lesser extent by the gastrointestinal tract. The mean excretion in the urine (+/-SD) at 48 h after injection was 58.3 +/- 5.4 percentage of the injected activity corrected for decay to the time of injection. The highest absorbed doses were received by the excretory organs (i.e., the urinary bladder and gallbladder wall). The average effective dose of (99m)Tc-RP527 was estimated to be 0.0095 mSv/MBq. CONCLUSION: The biodistribution of (99m)Tc-RP527 revealed low lung, myocardial, and liver uptake, which allowed early imaging of the supradiaphragmatic region with a favorable dosimetry (including effective dose) for administered activities required for SPECT imaging.

Adult↗