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ABSTRACT: Although lymphomas are very chemosensitive, 50% of patients with aggressive non-Hodgkin lymphoma (NHL) are not cured with standard first-line treatment. This consists of six cycles of doxorubicin, vincristine, prednisolone and cyclophosphamide (CHOP), recently complemented with rituximab. Preliminary studies show that PET mid-treatment is a good predictor of the remission status at the end of therapy. As patients with persistent FDG uptake after three cycles are unlikely to gain a complete remission, the remaining three cycles of chemotherapy are useless. We investigated the costs and benefits for the use of PET in this early treatment setting.
We conceived a model using a conventional arm where patients receive the full regimen of six cycles of CHOP [-rituximab] and an experimental algorithm where patients receive either six cycles (PET response) or only three cycles (PET non-response). Based on a patient sample (2004-2006), we calculated the costs for hospitalisation and treatment. We took into account all costs accrued (including overhead costs). We used a sensitivity analysis by varying the most important parameters.
With a PET price of 700 euro and CHOP price (per cycle) of 1,829 euro , we can conclude to cost saving of 1,879 euro per patient. The PET price can increase up to 2,580 euro and the cost for one cycle of CHOP can decrease to 500 euro per cycle before cost savings are nil. The percentage of non-responders may be as low as 10%. The implementation of rituximab in first-line therapy only increases benefit (4,900 euro/pt).
We conclude to substantial cost savings if management of NHL patients is based on mid-treatment PET scan. The economical data we used seem to be comparable to those published in other European studies. Implementation of Mabthera in first line only increases cost savings.
European journal of nuclear medicine and molecular imaging 07/2008; 35(6):1074-80. · 4.99 Impact Factor
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ABSTRACT: We have conjugated S,S'-bis-trityl-N-BOC-N'-acetic acid-1,2-ethylenedicysteamine, a protected bis-amino-bis-thiol (BAT) tetraligand, with 2-(4'-aminophenyl)-1,3-benzothiazole, a derivative of thioflavin-T with known affinity for amyloid. The conjugate was efficiently labelled with (99m)Tc by heating of the protected precursor in diluted hydrochloric acid followed by neutralization and heating in the presence of (99m)Tc-tartrate. It was demonstrated that the (99m)Tc-BAT-phenylbenzothiazole conjugate binds in vitro to amyloid beta present in postmortem brain slices of Alzheimer's patients. Despite its high lipophilicity and neutral character, the radiolabelled conjugate did not cross the blood-brain barrier to a sufficient degree and therefore is not useful for detection of Alzheimer's disease. Further evaluation of this (99m)Tc-labelled tracer agent could elucidate its potential usefulness to visualize amyloid plaques in peripheral amyloidosis.
Bioorganic & Medicinal Chemistry Letters 12/2007; 17(22):6086-90. · 2.55 Impact Factor
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Clinical Nuclear Medicine 06/2007; 32(5):393-5. · 3.67 Impact Factor
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ABSTRACT: To study fluorodeoxyglucose (FDG) deposition in different vascular beds and in the large joints of patients with isolated polymyalgia rheumatica (PMR), and to investigate whether there is a relation between FDG-positron emission tomography (PET) results and risk of relapse.
All consecutive patients with isolated PMR underwent a FDG-PET scan before treatment with steroids was started and--if logistics allowed--at 3 and 6 months. PET scans were scored at seven different vascular areas and a total vascular score (TVS) was calculated, ranging from 0 to 21. FDG uptake in the shoulders, the hips and the processi spinosi of the vertebrae was scored as 0 (no uptake), 1 (moderate uptake) or 2 (intense uptake).
Thirty-five patients entered the study. At diagnosis, vascular FDG uptake was noted in 11 patients (31%), predominantly at the subclavian arteries. Mean TVS was low. FDG uptake in the shoulders was noted in 94% of patients, in the hips in 89% and in the processi spinosi of the vertebrae in 51%. The intensity of FDG uptake in the large vessels or in the shoulders, hips or processi spinosi did not correlate with the risk of relapse.
Only one in three patients has an (moderately) increased vascular FDG uptake, especially in the subclavian arteries. The vast majority has inflammation of shoulders and hips, and half of them have increased FDG-uptake at the processi spinosi. Results of FDG-PET scans in patients with PMR did not correlate with their risk of relapse.
Rheumatology 05/2007; 46(4):672-7. · 4.06 Impact Factor
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ABSTRACT: Integrated positron emission tomography (PET) and computed tomography (CT) is a new imaging modality offering anatomic and metabolic information. The purpose was to evaluate retrospectively the accuracy of integrated PET-CT in the staging of a suggestive lung lesion, comparing this with the accuracy of CT alone, PET alone and visually correlated PET-CT. Fifty patients undergoing integrated PET-CT for staging of a suggestive lung lesion were studied. Their tumor, node, metastasis (TNM) statuses were determined with CT, PET, visually correlated PET-CT and integrated PET-CT. These TNM stages were compared with the surgical TNM status. Integrated PET-CT was the most accurate imaging technique in the assessment of the TNM status. Integrated PET-CT predicted correctly the T status, N status, M status and TNM status in, respectively, 86%, 80%, 98%, 70% versus 68%, 66%,88%, 46% with CT, 46%, 70%, 96%, 30% with PET and 72%, 68%, 96%, 54% with visually correlated PET-CT. T status and N status were overstaged, respectively, in 8% and 16% with integrated PET-CT, in 20% and 28% with CT, in 16% and 20% with PET, in 12% and 20% with visually correlated PET-CT and understaged in 6% and 4% with integrated PET-CT, versus 12% and 6% with CT, 38% and 10% with PET and 12% with visually correlated PET-CT. Integrated PET-CT improves the staging of lung cancer through a better anatomic localization and characterization of lesions and is superior to CT alone and PET alone. If this technique is not available, visual correlation of PET and CT can be a valuable alternative.
European Radiology 02/2007; 17(1):23-32. · 3.22 Impact Factor
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ABSTRACT: [(11)C]Methionine (MET) PET imaging is a sensitive technique for visualizing primary brain tumors and recurrence/progression after therapy. The aim of this study was to evaluate the relationship between the uptake of MET and histopathologic grading and to investigate the prognostic value of the tracer, in both settings.
Cerebral uptake of MET was determined in 52 patients: in 26 patients for primary staging (group A) and 26 patients with suspected brain tumor recurrence/progression after therapy (group B). Semiquantitative methionine uptake indices (UI) defined by the tumor (maximum)-to-background ratio was correlated with tumor grade and final outcome.
Overall median survival was 34.9 months. MET showed pathologically increased uptake in 41 of 52 scans. Although a weak linear correlation between MET uptake and grading was observed (R = 0.38, P = .028), analysis of variance showed no significant differences in MET UI between tumor grades for either group A or B. Benign and grade I lesions showed significant difference in MET uptake in comparison with higher grade lesions (P = .006). Using Kaplan-Meier survival analysis, no thresholds could be found at which MET was predictive for survival. Proportional hazard regression showed that only WHO grading class (low versus high) was predictive of survival (P = .015).
Interindividual MET uptake variability does not allow noninvasive grading on an individual patient basis. Moreover, there is no significant prognostic value in studying maximal methionine UI in brain tumors. The clinical use of MET should therefore be primarily focused on questions such as detection of recurrence, biopsy guidance, and radiation therapy target volume delineation.
American Journal of Neuroradiology 09/2006; 27(7):1432-7. · 2.93 Impact Factor
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ABSTRACT: The presence of lymph node involvement (N) and distant metastasis (M) in patients with invasive bladder carcinoma is a major determinant of survival and, therefore, a pivotal element in the therapeutic management. The aim of this prospective study was to evaluate the use of( 18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in this indication.
Whole-body FDG-PET and computed tomography (CT) were performed in 55 patients with non-metastatic invasive bladder cancer for preoperative staging. Correlative imaging of PET with CT was performed, leading to a PET(CT) result. The imaging results were compared with the gold standard, consisting of histopathology (lymphadenectomy, guided biopsy) or clinical follow-up for 12 months, and related to overall survival using the Kaplan-Meier method.
The gold standard was available in 40 patients and indicated NM-positive disease in 15 patients (12 N lesions, 8 M lesions), and NM-negative disease in 25 patients. For the diagnosis of NM-positive disease, the sensitivity, specificity and accuracy of PET(CT) were 60%, 88% and 78%, respectively. Diagnostic discordances between PET(CT) and CT alone were found in 9/40 patients, among whom PET was correct in six (15%): three with true-positive and one with true-negative distant metastases, and two with true-negative lymph nodes. Median survival time of patients in whom PET(CT) indicated NM-positive disease was 13.5 months, compared with 32.0 months in the patients with a NM-negative PET(CT) (p=0.003).
Addition of metabolism-based information provided by FDG-PET to CT in the preoperative staging of invasive bladder carcinoma yields a high diagnostic and prognostic accuracy.
European journal of nuclear medicine and molecular imaging 01/2006; 32(12):1412-7. · 4.99 Impact Factor
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ABSTRACT: Three cyclic polyamines, namely 1,4,7-triazacyclononane, 1,4,7,10-tetraazacyclo-dodecane (cyclen) and 1,4,8,11-tetraazacyclotetradecane (cyclam), were evaluated as potential ligands for complexation of a technetium(I) tricarbonyl core. They can be used as bifunctional chelating agents for labelling bioactive compounds. Each of the three ligands forms a positively charged technetium tricarbonyl complex in high yield but heating is required to promote complex formation. The charge of the 99mTc(I)tricarbonyl labelled derivatives was confirmed using electrophoresis, and radio-LC–MS supports their proposed chemical identity. After i.v. injection in mice, the compounds were rapidly cleared from the blood by the hepatobiliary or urinary pathway depending on their lipophilicity. Copyright © 2005 John Wiley & Sons, Ltd.
Journal of Labelled Compounds 11/2005; 48(14):1003 - 1011.
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ABSTRACT: (18)F-fluoro-deoxyglucose positron emission tomography (FDG PET) can aid to predict AD in an early stage. The aim of this study was to estimate the economic effects of incorporating FDG PET in the diagnostic work-up of AD in a Belgian and European setting. A decision tree analysis was followed comparing a conventional algorithm using diagnostic clinical criteria and one that also incorporates PET. Major outcome terms were overall cost per patient in either strategy; diagnostic accuracy and cost per accurate diagnosis. A sensitivity analysis was performed for four critical variables: cost of PET, sensitivity and specificity of PET and delay in cognitive decline because of appropriate medication. Cost-savings per accurate diagnosis ranged from 623-6110 Euro in favour of the proposed algorithm with PET. For the same cost, more accurate diagnoses were made, resulting in benefit for patients and society. The positive results were maintained over a wide range of values for the critical variables and were expandable to other European countries with a similar health system. Therefore, incorporation of FDG PET into the clinical diagnostic work up of patients with early symptoms of cognitive decline can be advocated.
European Journal of Neurology 05/2005; 12(4):254-63. · 3.69 Impact Factor
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ABSTRACT: This study aimed to evaluate tumour hypoxia by comparing [(18)F]Fluoromisonidazole uptake measured using positron emission tomography ([(18)F]FMISO-PET) with immunohistochemical (IHC) staining techniques. Syngeneic rhabdomyosarcoma (R1) tumour pieces were transplanted subcutaneously in the flanks of WAG/Rij rats. Tumours were analysed at volumes between 0.9 and 7.3 cm(3). Hypoxic volumes were defined using a 3D region of interest on 2 h postinjection [(18)F]FMISO-PET images, applying different thresholds (1.2-3.0). Monoclonal antibodies to pimonidazole (PIMO) and carbonic anhydrase IX (CA IX), exogenous and endogenous markers of hypoxia, respectively, were used for IHC staining. Marker-positive fractions were microscopically measured for each tumour, and hypoxic volumes were calculated. A heterogeneous distribution of hypoxia was observed both with histology and [(18)F]FMISO autoradiography. A statistically significant correlation (P<0.05) was obtained between the hypoxic volumes defined with [(18)F]FMISO-PET and the volumes derived from the PIMO-stained tumour sections (r=0.9066; P=0.0001), regardless of the selected threshold between 1.4 and 2.2. A similar observation was made with the CA IX staining (r=0.8636; P=0.0006). The relationship found between [(18)F]FMISO-PET and PIMO- and additionally CA IX-derived hypoxic volumes in rat rhabdomyosarcomas indicates the value of the noninvasive imaging method to measure hypoxia in whole tumours.
British Journal of Cancer 11/2004; 91(11):1947-54. · 5.04 Impact Factor
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ABSTRACT: A comparative study was carried out on two promising presynaptic dopamine transporter single-photon emission tomography (SPECT) radioligands with a fast pharmacokinetic profile, 123I-FP-beta-CIT (FP) and 99mTc-TRODAT-1 (TR), in order to assess their differential diagnostic power in early parkinsonism and their sensitivity for detection of disease progression. This cross-sectional study was conducted on 96 patients with early-stage parkinsonism referred in a tertiary clinical setting. Mean disease duration was 2.0+/-1.3 years, and patients had a modified Hoehn and Yahr (H&Y) stage of 1-2 (average 1.2). Forty-seven patients received TR, and 49 received FP. In both groups, ten patients with normal presynaptic function were included as a control population; all other patients were clinically diagnosed as having idiopathic Parkinson's disease. Groups were matched for gender, age, disease duration and modified H&Y stage. Triple-head gamma camera SPECT was analysed using a semiquantitative index of transporter binding (BI). Discriminant analysis with cross-validation resulted in a maximal classification accuracy for FP of 93% (sensitivity 95% and specificity 86%) for the contralateral putamen BI. For TR, the corresponding values were 87% accuracy, 92% sensitivity and 70% specificity. For FP, disease duration was correlated with both the putamen BI (-8.8%/year, rho=-0.41, P=0.025) and the putamen/caudate ratio (-7.4%/year, rho=-0.51, P=0.004), but for TR no significant correlation was found (all P values >0.5). In conclusion, both FP and TR show high sensitivity in a clinically relevant setting, but FP has superior accuracy for early differential diagnosis of idiopathic parkinsonism and non-degenerative extrapyramidal disorders, as well as better sensitivity for disease follow-up.
European journal of nuclear medicine and molecular imaging 08/2004; 31(8):1119-27. · 4.99 Impact Factor
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ABSTRACT: Positron emission tomography (PET) using the positron emitting glucose analogue 18F-fluorodeoxyglucose (FDG) has emerged as a useful metabolism-based wholebody imaging tool for gastro-esophageal cancer diagnosis and follow up. Most large cancer centers worldwide are now equipped for PET (or even PET-CT). Therefore, there is a growing need for a clear definition of the relative position of PET within the currently available diagnostic modalities. Significant scientific data indicate that FDG-PET adds clinically useful information to the information obtained by standard means (mainly CT and endoscopic ultrasound) throughout the different phases of clinical patient management: 1) at initial diagnosis: PET detects more frequently distant lymph node involvement and organ metastases compared to conventional diagnostics, allowing a more accurate selection of the most appropriate treatment; 2) during chemotherapy: semi-quantitative FDG-PET allows early identification of non-responding patients. Indeed, the metabolic response as measured by serial FDG-PET can be used to predict the clinical and histopathological response. Moreover, the PET-response seems to be related to overall and disease free survival; 3) after a treatment: FDG-PET allows accurate assessment of the residual tumor load; 4) in the follow up: FDG-PET allows accurate detection and restaging of recurrent disease.
The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... 07/2004; 48(2):96-108.
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L Herbots,
F Maes,
J D'hooge,
P Claus,
S Dymarkowski,
P Mertens, L Mortelmans,
B Bijnens,
J Bogaert,
F E Rademakers,
G R Sutherland
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ABSTRACT: Strain rate imaging (SRI) is a new ultrasound (US) approach to the quantification of regional myocardial deformation. It previously has been validated in vitro and in vivo against other imaging techniques. However, in all such studies, only peak strain values were compared, and the temporal evolution of the strain curve was not studied. Yet, it is the temporal evolution of the strain curves that contains the more important clinical information (e.g., asynchrony, viability, etc). Thus, the aim of this study was to compare the evolution of strain during the complete cardiac cycle as measured by US SRI, US grey-scale M-mode and magnetic resonance imaging (MRI). In 10 healthy volunteers and 20 patients with chronic ischaemic heart disease, radial deformation of the inferolateral segment of the left ventricle was measured by US SRI, US M-mode and MRI. The correspondence of the temporal characteristics of these strain curves were compared by defining an intraclass correlation coefficient (ICC). In healthy volunteers, an overall good agreement (mean ICC: 0.75 and 0.63 for systole and diastole) was found between the different methods. However, in patients with abnormal segmental deformation and low peak strain values, the agreement was less (mean ICC: 0.42 and 0.32), but remained within acceptable limits for clinical decision making. Myocardial deformation measurements using SRI correlated well with MRI and US M-mode measurements throughout the complete cardiac cycle.
Ultrasound in Medicine & Biology 06/2004; 30(5):591-8. · 2.29 Impact Factor
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European Radiology 04/2004; 14(5):926-927. · 3.22 Impact Factor
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S Stroobants,
J Goeminne,
M Seegers,
S Dimitrijevic,
P Dupont,
J Nuyts,
M Martens,
B van den Borne,
P Cole,
R Sciot,
H Dumez,
S Silberman, L Mortelmans,
A van Oosterom
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ABSTRACT: Imatinib mesylate (Glivec, formerly STI571) is the first effective systemic treatment for gastrointestinal stromal tumours (GISTs). Major changes in tumour volume, however, tend to occur late after the start of treatment. The aim of this study was to evaluate if [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) can be used for the early evaluation of response to imatinib mesylate treatment in soft-tissue sarcomas (STS). 21 patients (17 GIST, 4 other STS) underwent FDG-PET imaging prior to and 8 days after the start of treatment. PET response (European Organization for Research and Treatment (EORTC) guidelines) was observed in 13 GISTs (11 Complete Responders, 2 partial responders. Subsequent computerised tomography (CT) response Response Evaluation Criteria in Solid Tumours (RECIST) was observed in 10 of these patients after a median follow up of 8 weeks. Stable or progressive disease was observed on PET in 8 patients and none of them achieved a response on CT. PET response was also associated with a longer progression-free survival (PFS) (92% versus 12% at 1 year, P=0.00107). We conclude that FDG-PET is an early and sensitive method to evaluate an early response to imatinib treatment.
European Journal of Cancer 10/2003; 39(14):2012-20. · 5.54 Impact Factor
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ABSTRACT: 99mTc-exametazime (99mTc-d,l-HMPAO, 99mTc-d,l-hexamethylpropyleneamine oxime) is a neutral rather unstable complex of short-lived 99mTc (t(1/2)=6 h) with the d,l-isomer (mixture of D,D- and L,L-isomers) of a bis-amine bis-oxime tetraligand. It is widely used for measurement of regional cerebral perfusion in nuclear medicine. The meso-isomer (D,L-form) should not be present in a preparation as it is not retained in brain and thus does not provide clinically useful information. Meso-HMPAO is removed from the ligand during the synthesis procedure by repeated recrystallization, but can still be present as impurity in d,l-isomer. Due to the lack of a suitable chromatographic method for analysis of the isomeric purity of 99mTc-exametazime preparations, United States Pharmacopoeia 25 (USP 25) prescribes a biological test in rats for quality control purpose. In this study, we developed a suitable high-performance liquid chromatography (HPLC) method which allows to demonstrate the relative amounts of d,l- and meso-isomer in 99mTc-exametazime and so obviates the need for a biodistribution test in animals as part of the quality control. Due to the low concentrations in which 99mTc-d,l-HMPAO is obtained (typically 2-6 ng/ml), confirmation of the identity of 99mTc-d,l-HMPAO in the monograph of the European Pharmacopoeia is now performed only indirectly by TLC and assessment of its retention time on RP-HPLC. To investigate the potential of radio-LC-MS for assessment of the identity of 99mTc-exametazime, 99mTc-d,l-HMPAO and 99mTc-meso-HMPAO prepared using a Tc-rich eluate were analyzed using a radio-LC-MS system equipped with a time-of-flight mass spectrometer with electrospray ionization. The main peak in the radiometric channel coincided with the molecular ion mass of 99mTc-d,l-HMPAO in the mass spectrometer channel and the measured accurate mass differed only by 0.26 ppm from the theoretical mass. The identity of 99mTc-meso-HMPAO was also confirmed. Thus, radio-LC-MS allowed to obtain strong evidence for the structure of 99mTc-d,l-HMPAO and 99mTc-meso-HMPAO at nanomolar concentration. It is concluded that radio-LC-MS can become a sensitive aid in quality control of "no carrier added" radiopharmaceutical preparations.
Journal of Pharmaceutical and Biomedical Analysis 09/2003; 32(4-5):679-85. · 2.97 Impact Factor
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European journal of nuclear medicine and molecular imaging 06/2003; 30(5):796-7. · 4.99 Impact Factor
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ABSTRACT: The differentiation between differing regional ischaemic substrates is crucial for decision-making in patients with coronary artery disease. This study demonstrates that quantification of dobutamine stress echocardiography using ultrasonic strain measurement has the potential to identify three differing regional ischaemic substrates (ischaemic, stunned and scarred) in the same patient. The data were validated by traditional analysis of dobutamine stress echo, coronary angiography and correlative quantitative positron emission tomography information.
European Heart Journal – Cardiovascular Imaging 04/2003; 4(1):23-8. · 2.32 Impact Factor
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ABSTRACT: S,S′-bis-trityl-N-BOC-1,2-ethylenedicysteamine (S,S′-bis-trityl-N-BOC–BAT) was conjugated to 2-nitroimidazole (NIM) through a propylene spacer in order to provide a precursor for a potential technetium-99 m labelled hypoxia tracer. For labelling with technetium-99 m, a two-step one-pot procedure was developed consisting of deprotection of the ligand by heating in mild acidic conditions and subsequent exchange labelling in the presence of SnCl2, tartrate and 99mTcO.The labelling reaction mixture was analyzed using electrospray radio-LC–MS and the observed mass spectrum corresponding to the main radiometric peak was in accordance with the predicted structure of oxo–Tc(V)–NIM–BAT.99mTc–NIM–BAT was purified using RP–HPLC and its biodistribution was evaluated in normal mice at 10 min and 4 h p.i. 99mTc–NIM–BAT was cleared from plasma mainly by hepatobiliary excretion. Copyright © 2003 John Wiley & Sons, Ltd.
Journal of Labelled Compounds 03/2003; 46(6):575 - 585.
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ABSTRACT: In a non-surgical porcine coronary stenosis model resulting in chronic left ventricle dysfunction, we aimed in this study to evaluate the potential of magnetic resonance imaging (MRI) to distinguish dysfunctional but viable from necrotic myocardium by using multiple levels of dobutamine inotropic stimulation during a cine MRI protocol (F.P. van Rugge et al. Circulation 1994; 90: 127-138). We compared our results with histopathology. We were able to demonstrate a biphasic effect at increasing doses of dobutamine in a subgroup of animals with a high-grade coronary stenosis, while in another subgroup the coronary stenosis produced a chronic myocardial infarction, in which no functional recovery could be obtained. In this experimental protocol, dual dose dobutamine MRI proved to be an accurate and reproducible technique to perform viability studies in chronic obstructive coronary artery disease. It permits distinguishing chronic ischemic, but viable myocardium from infarcted tissue. The detection of chronically underperfused but potentially salvageable myocardium is of significant clinical importance since it may aid in determining which patients are eligible for revascularization.
The International Journal of Cardiovascular Imaging 03/2003; 19(1):63-72. · 2.29 Impact Factor
