| 1. |
- Rizvi, Saiyada N. F., et al.
(författare)
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Biodistribution, radiation dosimetry and scouting of 90Y-ibritumomab tiuxetan therapy in patients with relapsed B-cell non-Hodgkin's lymphoma using 89Zr-ibritumomab tiuxetan and PET
- 2012
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 39:3, s. 512-520
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Positron emission tomography (PET) with Zr-89-britumomab tiuxetan can be used to monitor biodistribution of Y-90-ibritumomab tiuxetan as shown in mice. The aim of this study was to assess biodistribution and radiation dosimetry of 90Y-ibritumomab tiuxetan in humans on the basis of Zr-89-ibritumomab tiuxetan imaging, to evaluate whether co-injection of a therapeutic amount of Y-90-ibritumomab tiuxetan influences biodistribution of Zr-89-ibritumomabtiuxetan and whether pre-therapy scout scans with Zr-89-ibritumomab tiuxetan can be used to predict biodistribution of Y-90-ibritumomab tiuxetan and the dose-limiting organ during therapy. Methods: Seven patients with relapsed B-cell non-Hodgkin's lymphoma scheduled for autologous stem cell transplantation underwent PET scans at 1, 72 and 144 h after injection of similar to 70 MBq Zr-89-ibritumomab tiuxetan and again 2 weeks later after co-injection of 15 MBq/kg or 30 MBq/kg Y-90-britumomab tiuxetan. Volumes of interest were drawn over liver, kidneys, lungs, spleen and tumours. Ibritumomab tiuxetan organ absorbed doses were calculated using OLINDA. Red marrow dosimetry was based on blood samples. Absorbed doses to tumours were calculated using exponential fits to the measured data. Results: The highest Y-90 absorbed dose was observed in liver (3.2 +/- 1.8 mGy/MBq) and spleen (2.9 +/- 0.7 mGy/MBq) followed by kidneys and lungs. The red marrow dose was 0.52 +/- 0.04 mGy/MBq, and the effective dose was 0.87 +/- 0.14 mSv/MBq. Tumour absorbed doses ranged from 8.6 to 28.6 mGy/MBq. Correlation between predicted pre-therapy and therapy organ absorbed doses as based on Zr-89-ibritumomab tiuxetan images was high (Pearson correlation coefficient r=0.97). No significant difference between pre-therapy and therapy tumour absorbed doses was found, but correlation was lower (r=0.75). Conclusion: Biodistribution of Zr-89-ibritumomab tiuxetan is not influenced by simultaneous therapy with Y-90-ibritumomab tiuxetan, and Zr-89-ibritumomab tiuxetan scout scans can thus be used to predict biodistribution and dose-limiting organ during therapy. Absorbed doses to spleen were lower than those previously estimated using In-111-ibritumomab tiuxetan. The dose-limiting organ in patients undergoing stem cell transplantation is the liver.
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| 2. |
- Danad, Ibrahim, et al.
(författare)
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Carotid artery intima-media thickness, but not coronary artery calcium, predicts coronary vascular resistance in patients evaluated for coronary artery disease
- 2012
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Ingår i: European Heart Journal: Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 13:4, s. 317-323
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Tidskriftsartikel (refereegranskat)abstract
- Aims There is growing evidence that coronary artery disease (CAD) affects not only the conduit epicardial coronary arteries, but also the microvascular coronary bed. Moreover, coronary microvascular dysfunction (CMVD) often precedes the stage of clinically overt epicardial CAD. Coronary artery calcium (CAC) and carotid intima-media thickness (C-IMT) measured with computed tomography (CT) and ultrasound, respectively, are among the available techniques to non-invasively assess atherosclerotic burden. An increased CAC score and C-IMT have also been associated with CMVD. It is therefore of interest to explore and compare the potential of CAC against C-IMT to predict minimal coronary vascular resistance (CVR). Methods and results We evaluated 120 patients (mean age 56 +/- 9 years, 58 men) without a documented history of CAD in whom and results obstructive CAD was excluded. All patients underwent C-IMT measurements, CAC scoring, and vasodilator stress O-15-water positron emission tomography (PET)/CT, during which the coronary flow reserve (CFR) and minimal CVR were analysed. Minimal CVR increased significantly with increasing tertiles of C-IMT (22 +/- 6, 27 +/- 11, and 28 +/- 9 mmHg mL(-1) min(-1) g(-1), P < 0.01), whereas the CFR was comparable across all C-IMT groups (P = 0.50). Minimal CVR increased significantly with an increase in CAC score (23 +/- 9, 27 +/- 8, 32 +/- 10, and 32 +/- 7 mmHg mL(-1) min(-1) g(-1). P < 0.01), whereas the CFR did not show a significant decrease with higher CAC scores (P = 0.18). Multivariable regression analysis revealed that C-IMT (P = 0.03), but not CAC, was independently associated with minimal CVR. Conclusion C-IMT, but not CAC score, independently predicts minimal CVR in patients with multiple cardiovascular risk factors and suspected of CAD.
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| 3. |
- Danad, Ibrahim, et al.
(författare)
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Coronary risk factors and myocardial blood flow in patients evaluated for coronary artery disease : a quantitative [15O]H2O PET/CT study
- 2012
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 39:1, s. 102-112
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThere has been increasing interest in quantitative myocardial blood flow (MBF) imaging over the last years and it is expected to become a routinely used technique in clinical practice. Positron emission tomography (PET) using [15O]H2O is the established gold standard for quantification of MBF in vivo. A fundamental issue when performing quantitative MBF imaging is to define the limits of MBF in a clinically suitable population. The aims of the present study were to determine the limits of MBF and to determine the relationship among coronary artery disease (CAD) risk factors, gender and MBF in a predominantly symptomatic patient cohort without significant CAD.MethodsA total of 128 patients (mean age 54 ± 10 years, 50 men) with a low to intermediate pretest likelihood of CAD were referred for noninvasive evaluation of CAD using a hybrid PET/computed tomography (PET/CT) scanner. MBF was quantified with [15O]H2O at rest and during adenosine-induced hyperaemia. Obstructive CAD was excluded in these patients by means of invasive or CT-based coronary angiography.ResultsGlobal average baseline MBF values were 0.91 ± 0.34 and 1.09 ± 0.30 ml·min−1·g−1 (range 0.54–2.35 and 0.59–2.75 ml·min−1·g−1) in men and women, respectively (p < 0.01). However, no gender-dependent difference in baseline MBF was seen following correction for rate–pressure product (0.98 ± 0.45 and 1.09 ± 0.30 ml·min−1·g−1 in men and women, respectively; p = 0.08). Global average hyperaemic MBF values were 3.44 ± 1.20 ml·min−1·g−1 in the whole study population, and 2.90 ± 0.85 and 3.78 ± 1.27 ml·min−1·g−1 (range 1.52–5.22 and 1.72–8.15 ml·min−1·g−1) in men and women, respectively (p < 0.001). Multivariate analysis identified male gender, age and body mass index as having an independently negative impact on hyperaemic MBF.ConclusionGender, age and body mass index substantially influence reference values and should be corrected for when interpreting hyperaemic MBF values.
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| 4. |
- de Langen, Adrianus J, et al.
(författare)
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Monitoring response to antiangiogenic therapy in non-small cell lung cancer using imaging markers derived from PET and dynamic contrast-enhanced MRI
- 2011
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 52:1, s. 48-55
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Tidskriftsartikel (refereegranskat)abstract
- With antiangiogenic agents, tumor shrinkage may be absent, despite survival benefit. The present study assessed the predictive value of molecular imaging for the identification of survival benefit during antiangiogenic treatment with bevacizumab and erlotinib in patients with advanced non–small cell lung cancer.Methods:Patients were evaluated using an imaging protocol including CT, 18F-FDG PET, H215O PET, and dynamic contrast-enhanced MRI to derive measurements on tumor size, glucose metabolism, perfusion, and microvascular permeability. The percentage change in imaging parameters after 3 wk of treatment as compared with baseline was calculated and correlated with progression-free survival (PFS).Results:Forty-four patients were included, and 40 underwent CT and 18F-FDG PET at both time points. Complete datasets, containing all imaging modalities, were available for 14 patients. Bevacizumab and erlotinib treatment resulted in decreased metabolism, perfusion, and tumor size. A decrease in standardized uptake value or tumor perfusion of more than 20% at week 3 was associated with longer PFS (9.7 vs. 2.8 mo, P = 0.01, and 12.5 vs. 2.9 mo, P = 0.009, respectively). Whole-tumor Ktrans (the endothelial transfer constant) was not associated with PFS, but patients with an increase of more than 15% in the SD of tumor Ktrans values—that is, an increase in regions with low or high Ktrans values—after 3 wk had shorter PFS (2.3 vs. 7.0 mo, P = 0.008). A partial response, according to the response evaluation criteria in solid tumors (RECIST), at week 3 was also associated with prolonged PFS (4.6 vs. 2.9 mo, P = 0.017). However, 40% of patients with a partial response as their best RECIST response still had stable disease at week 3. In these cases tumor perfusion was already decreased and Ktrans heterogeneity showed no increase, indicating that the latter parameters seem to be more discriminative than RECIST at the 3-wk time point.Conclusion:PET and dynamic contrast-enhanced MRI were able to identify patients who benefit from bevacizumab and erlotinib treatment. Molecular imaging seems to allow earlier response evaluation than CT.
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| 5. |
- Hommes, JW, et al.
(författare)
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High density lipoproteins mediate in vivo protection against staphylococcal phenol-soluble modulins
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 15357-
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus virulence has been associated with the production of phenol-soluble modulins (PSMs). These PSMs have distinct virulence functions and are known to activate, attract and lyse neutrophils. These PSM-associated biological functions are inhibited by lipoproteins in vitro. We set out to address whether lipoproteins neutralize staphylococcal PSM-associated virulence in experimental animal models. Serum from both LCAT an ABCA1 knockout mice strains which are characterised by near absence of high-density lipoprotein (HDL) levels, was shown to fail to protect against PSM-induced neutrophil activation and lysis in vitro. Importantly, PSM-induced peritonitis in LCAT−/− mice resulted in increased lysis of resident peritoneal macrophages and enhanced neutrophil recruitment into the peritoneal cavity. Notably, LCAT−/− mice were more likely to succumb to staphylococcal bloodstream infections in a PSM-dependent manner. Plasma from homozygous carriers of ABCA1 variants characterized by very low HDL-cholesterol levels, was found to be less protective against PSM-mediated biological functions compared to healthy humans. Therefore, we conclude that lipoproteins present in blood can protect against staphylococcal PSMs, the key virulence factor of community-associated methicillin resistant S. aureus.
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| 6. |
- Lubberink, Mark, et al.
(författare)
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Validity of Simplified 3′-Deoxy-3′-[18F]Fluorothymidine Uptake Measures for Monitoring Response to Chemotherapy in Locally Advanced Breast Cancer
- 2012
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Ingår i: Molecular Imaging and Biology. - : Springer Science and Business Media LLC. - 1536-1632 .- 1860-2002. ; 14:6, s. 777-782
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:Positron emission tomography using 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) has been suggested as a means for monitoring response to chemotherapy. The aim of this study was to evaluate the validity of simplified uptake measures for assessing response to chemotherapy using [18F]FLT in locally advanced breast cancer (LABC).Procedures:Fifteen LABC patients underwent dynamic [18F]FLT scans both prior to and after the first cycle of chemotherapy with fluorouracil, epirubicin or doxorubicin, and cyclophosphamide. The net uptake rate constant of [18F]FLT, K i , determined by non-linear regression (NLR) of an irreversible two-tissue compartment model was used as the gold standard. In addition to Patlak graphical analysis, standardised uptake values (SUV) and tumour-to-whole blood ratio (TBR) were used for analysing [18F]FLT data. Correlations and relationships between simplified uptake measures and NLR before and after chemotherapy were assessed using regression analysis.Results: No significant differences in both pre- and post-chemotherapy relationships between any of the simplified uptake measures and NLR were found. However, changes in SUV between baseline and post-therapy scans showed a significant negative bias and slope less than one, while TBR did not.Conclusions:In LABC, TBR instead of SUV may be preferred for monitoring response to chemotherapy with [18F]FLT.
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| 7. |
- Oprea-Lager, Daniela E, et al.
(författare)
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Dual-Phase PET-CT to Differentiate [(18)F]Fluoromethylcholine Uptake in Reactive and Malignant Lymph Nodes in Patients with Prostate Cancer
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10, s. e48430-
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate whether time-trends of enhanced [(18)F]Fluoromethylcholine ([(18)F]FCH) in lymph nodes (LN) of prostate cancer (PCa) patients can help to discriminate reactive from malignant ones, and whether single time point standardized uptake value (SUV) measurements also suffice.PROCEDURES: 25 PCa patients with inguinal (presumed benign) and enlarged pelvic LN (presumed malignant) showing enhanced [(18)F]FCH uptake at dual-phase PET-CT were analyzed. Associations between LN status (benign versus malignant) and SUV(max) and SUV(meanA50), determined at 2 min (early) and 30 min (late) post injection, were assessed. We considered two time-trends of [(18)F]FCH uptake: type A (SUV early > SUV late) and type B (SUV late ≥ SUV early). Histopathology and/or follow-up were used to confirm the assumption that LN with type A pattern are benign, and LN with type B pattern malignant.RESULTS: Analysis of 54 nodes showed that LN status, time-trends, and 'late' (30 min p.i.) SUV(max) and SUV(meanA50) parameters were strongly associated (P<0.0001). SUV(max) relative difference was the best LN status predictor. All but one inguinal LN showed a decreasing [(18)F]FCH uptake over time (pattern A), while 95% of the pelvic nodes presented a stable or increasing uptake (pattern B) type.CONCLUSIONS: Time-trends of enhanced [(18)F]FCH uptake can help to characterize lymph nodes in prostate cancer patients. Single time-point SUV measurements, 30 min p.i., may be a reasonable alternative for predicting benign versus malignant status of lymph nodes, but this remains to be validated in non-enlarged pelvic lymph nodes.
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