Publications (41) View all
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Article: Re: Sarcoid-like reaction to malignancy on whole-body integrated 18F-FDG PET/CT: prevalence and disease pattern.
Clinical radiology 01/2010; 65(1):94-6; author reply 96-7. · 1.65 Impact Factor -
Article: Absolute quantification of [(11)C]docetaxel kinetics in lung cancer patients using positron emission tomography.
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ABSTRACT: Tumor resistance to docetaxel may be associated with reduced drug concentrations in tumor tissue. Positron emission tomography (PET) allows for quantification of radiolabeled docetaxel ([(11)C]docetaxel) kinetics and might be useful for predicting response to therapy. The primary objective was to evaluate the feasibility of quantitative [(11)C]docetaxel PET scans in lung cancer patients. The secondary objective was to investigate whether [(11)C]docetaxel kinetics were associated with tumor perfusion, tumor size, and dexamethasone administration. Thirty-four lung cancer patients underwent dynamic PET-computed tomography (CT) scans using [(11)C]docetaxel. Blood flow was measured using oxygen-15 labeled water. The first 24 patients were premedicated with dexamethasone. For quantification of [(11)C]docetaxel kinetics, the optimal tracer kinetic model was developed and a noninvasive procedure was validated. Reproducible quantification of [(11)C]docetaxel kinetics in tumors was possible using a noninvasive approach (image derived input function). Thirty-two lesions (size ≥4 cm(3)) were identified, having a variable net influx rate of [(11)C]docetaxel (range, 0.0023-0.0229 mL·cm(-3)·min(-1)). [(11)C]docetaxel uptake was highly related to tumor perfusion (Spearman's ρ = 0.815;P < 0.001), but not to tumor size (Spearman's ρ = -0.140; P = 0.446). Patients pretreated with dexamethasone showed lower [(11)C]docetaxel uptake in tumors (P = 0.013). Finally, in a subgroup of patients who subsequently received docetaxel therapy, relative high [(11)C]docetaxel uptake was related with improved tumor response. Quantification of [(11)C]docetaxel kinetics in lung cancer was feasible in a clinical setting. Variable [(11)C]docetaxel kinetics in tumors may reflect differential sensitivity to docetaxel therapy. Our findings warrant further studies investigating the predictive value of [(11)C]docetaxel uptake and the effects of comedication on [(11)C]docetaxel kinetics in tumors.Clinical Cancer Research 07/2011; 17(14):4814-24. · 7.74 Impact Factor -
Article: Biodistribution and radiation dosimetry of 11C-labelled docetaxel in cancer patients.
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ABSTRACT: Docetaxel is an important chemotherapeutic agent used for the treatment of several cancer types. As radiolabelled anticancer agents provide a potential means for personalized treatment planning, docetaxel was labelled with the positron emitter (11)C. Non-invasive measurements of [(11)C]docetaxel uptake in organs and tumours may provide additional information on pharmacokinetics and pharmacodynamics of the drug docetaxel. The purpose of the present study was to determine the biodistribution and radiation absorbed dose of [(11)C]docetaxel in humans. Biodistribution of [(11)C]docetaxel was measured in seven patients (five men and two women) with solid tumours using PET/CT. Venous blood samples were collected to measure activity in blood and plasma. Regions of interest (ROI) for various source organs were defined on PET (high [(11)C]docetaxel uptake) or CT (low [(11)C]docetaxel uptake). ROI data were used to generate time-activity curves and to calculate percentage injected dose and residence times. Radiation absorbed doses were calculated according to the MIRD method using OLINDA/EXM 1.0 software. Gall bladder and liver demonstrated high [(11)C]docetaxel uptake, whilst uptake in brain and normal lung was low. The percentage injected dose at 1 h in the liver was 47 +/- 9%. [(11)C]docetaxel was rapidly cleared from plasma and no radiolabelled metabolites were detected. [(11)C]docetaxel uptake in tumours was moderate and highly variable between tumours. The effective dose of [(11)C]docetaxel was 4.7 microSv/MBq. As uptake in normal lung is low, [(11)C]docetaxel may be a promising tracer for tumours in the thoracic region.European Journal of Nuclear Medicine 10/2010; 37(10):1950-8. · 4.53 Impact Factor -
Article: Quantitative parametric perfusion images using 15O-labeled water and a clinical PET/CT scanner: test-retest variability in lung cancer.
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ABSTRACT: Quantification of tumor perfusion using radioactive water (H(2)(15)O) and PET is a promising method for monitoring treatment with antiangiogenic agents. However, use of dynamic H(2)(15)O scans together with a fully 3-dimensional clinical PET/CT scanner needs to be validated. The purpose of the present study was to assess validity and reproducibility of dynamic H(2)(15)O PET/CT scans for measuring tumor perfusion and validate the quantitative accuracy of parametric perfusion images. Eleven patients with non-small cell lung cancer were included in this study. Patients underwent 2 dynamic H(2)(15)O (370 MBq) PET scans on the same day. During the first scan, arterial blood was withdrawn continuously. Input functions were derived from blood sampler data and the ascending aorta as seen in the images themselves (image-derived input function [IDIF]). Parametric perfusion images were computed using a basis function implementation of the standard single-tissue-compartment model. Volumes of interest (VOIs) were delineated on low-dose CT (LD-CT) and parametric perfusion images. VOIs could be accurately delineated on both LD-CT and parametric perfusion images. These parametric perfusion images had excellent image quality and quantitative accuracy when compared with perfusion values determined by nonlinear regression. Good correlation between perfusion values derived from the blood sampler input function and IDIF was found (Pearson correlation coefficient, r = 0.964; P < 0.001). Test-retest variability of tumor perfusion was 16% and 20% when delineated on LD-CT and parametric perfusion images, respectively. The use of ascending aorta IDIFs is an accurate alternative to arterial blood sampling for quantification of tumor perfusion. Image quality obtained with a clinical PET/CT scanner enables generation of accurate parametric perfusion images. VOIs delineated on LD-CT have the highest reproducibility, and changes of more than 16% in tumor perfusion are likely to represent treatment effects.Journal of Nuclear Medicine 10/2010; 51(11):1684-90. · 6.38 Impact Factor -
Article: Regional increase in P-glycoprotein function in the blood-brain barrier of patients with chronic schizophrenia: a PET study with [(11)C]verapamil as a probe for P-glycoprotein function.
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ABSTRACT: P-glycoprotein (P-gp), a major efflux pump in the blood-brain barrier (BBB) has a profound effect on entry of drugs, peptides and other substances into the central nervous system (CNS). The brain's permeability can be negatively influenced by modulation of the transport function of P-gp. Inflammatory mediators play a role in schizophrenia, and may be able to influence the integrity of the BBB, via P-gp modulation. We hypothesized that P-gp function in the BBB is changed in patients with schizophrenia. Positron-emission tomography was used to measure brain uptake of [(11)C]verapamil, which is normally extruded from the brain by P-gp. We found that patients with chronic schizophrenia under treatment with antipsychotic drugs compared with healthy controls showed a significant decrease in [(11)C]verapamil uptake in the temporal cortex, the basal ganglia, and the amygdala, and amygdalae, and a trend towards a significant decrease was seen throughout the brain. The decrease of [(11)C]verapamil uptake correlates with an increased activity of the P-gp pump. Increased P-gp activity may be a factor in drug resistance in schizophrenia, induced by the use of antipsychotic agents.Psychiatry Research 08/2010; 183(2):151-6. · 2.52 Impact Factor
