| 1. |
- Barta, Pavel, et al.
(författare)
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Circumventing the requirement of binding saturation for receptor quantification using interaction kinetic extrapolation
- 2011
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Ingår i: Nuclear medicine communications. - 0143-3636 .- 1473-5628. ; 32:9, s. 863-867
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Tidskriftsartikel (refereegranskat)abstract
- Quantification of the number of receptors per cell (NRPC) is important when assessing whether a tumor surface biomarker is suitable for medical imaging. One common method for NPRC quantification is to use a binding saturation assay, which is time consuming and requires large amounts of reagents. The aim of this study was to evaluate an alternative method based on kinetic extrapolation (KEX) and compare it with the classical manual saturation technique with regard to accuracy as well as time and reagent consumption. Epidermal growth factor receptor (EGFR) and HER2 receptor surface expression were quantified on five tumor cell lines using three (125)I-labeled and (131)I-labeled ligands (cetuximab and EGF for EGFR, trastuzumab for HER2 receptor) for both techniques. The KEX method involved interaction measurements in the LigandTracer, followed by KEX through computerized real-time interaction analysis to correct for nonsaturation on cells. Variability and NRPC estimates of the EGFR and HER2 receptor levels using the KEX method were comparable with the results from the classical saturation technique. However, the ligand consumption for the KEX method was 26-46% of the classical saturation technique. Furthermore, the KEX method reduced the workload radically. From the observations described in this study, we believe that the KEX method enables fast, credible, and easy NRPC quantification with a reduction in reagent consumption.
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| 2. |
- Bäck, Anna-Karin, 1971-, et al.
(författare)
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Renography with a semiautomated algorithm for diuretic decision 7 min postradiopharmaceutical administration : a feasibility study
- 2020
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Ingår i: Nuclear medicine communications. - : Lippincott Williams & Wilkins. - 0143-3636 .- 1473-5628. ; 41:10, s. 1018-1025
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The F+10 method for diuretic renography (diuretics given 10 min after the radiopharmaceutical) could be a time-conserving method. This method involves a 30-min dynamic acquisition where diuretics are administered only when necessary by the Nuclear Medicine technologist performing the examination. The purpose of this study was to assess the method's performance and to discover the optimal threshold of residual activity for a diuretic administration 7 min into the F+10 renography by reprocessing raw data from prior performed examinations with 20-min acquisitions without diuretics.METHODS: Retrospectively, raw data from 320 original examinations of adult patients performed from 2013 to 2015 were reprocessed into 7-min series and categorized as requiring diuretic or not. The diuretic decisions made by an expert panel were used as a reference. A receiver-operating characteristic curve was drawn to assess the optimal cutoff value for the residual renal activity. Sensitivity, specificity, positive and negative predictive values, as well as the Youden J index were calculated.RESULT: The experts classified 50% (160 examinations) as in need of diuretics. The receiver-operating characteristic curve demonstrated the theoretical optimal cutoff value at 7 min to be 94% of maximum activity (sensitivity 0.93, specificity 0.81, Youden J index 0.73). A clinically acceptable threshold is suggested to be 85% (sensitivity 0.99, specificity 0.59, Youden J index 0.58).CONCLUSION: Tc-mercaptoacetyltriglycine renography with the F+10 method and the threshold 85% for diuretic decision 7 min into the renography is a feasible and acceptable method in clinical practice.
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| 3. |
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| 4. |
- Edwards, David, et al.
(författare)
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99mTc-NC100668, an agent for imaging venous thromboembolism : The effect of anticoagulant or thrombolytic therapy on the uptake and retention of radioactivity in blood clots in vivo
- 2007
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Ingår i: Nuclear medicine communications. - : Ovid Technologies (Wolters Kluwer Health). - 0143-3636 .- 1473-5628. ; 28:1, s. 55-62
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose of this study was to evaluate the uptake of Tc-NC100668 into blood clots and elucidate the potential for medications commonly used to treat thromboembolism to interfere with the uptake and retention of Tc-NC100668. METHODS: Tc-NC100668 in vivo uptake and retention in a range of blood clot of various ages (up to 4 h old) and in the presence of anticoagulants or thrombolytic therapies was measured in a rat model of deep vein thrombosis. RESULTS: Tc-NC100668 was rapidly absorbed into and retained by blood clots and was not significantly affected by the presence of unfractionated or low molecular weight heparin or thrombin inhibitor. Tissue plasminogen activator reduced the uptake of Tc-NC100668 into blood clot by a factor of 3 when adjusted to allow for changes in the weight of the blood clot. CONCLUSIONS: This study has demonstrated that the uptake and retention of Tc-NC100668 into blood clots in the rat model of deep vein thrombosis is rapid and maintained over at least a 4 h post-injection period. It has been shown that Tc-NC100668 is retained in blood clots even in the presence of therapeutic doses of those anticoagulant and thrombolytic therapies typically used to treat pulmonary embolism and venous thrombosis.
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| 5. |
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| 6. |
- Sjöström, A, et al.
(författare)
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Direct astatination of a peptide, human epidermal growth factor, using nido-carborane as a prosthetic group
- 2000
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Ingår i: Nuclear medicine communications. - 0143-3636 .- 1473-5628. ; 21:6, s. 594-
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Recension (övrigt vetenskapligt/konstnärligt)abstract
- Purpose The aim of the study was to evaluate direct astatine labelling of proteins with the use of nido-carborane as prosthetic group for attachments of astatine. Methods: Human epidermal growth factor, hEGF, was conjugated to 7-(3-amino-propyl)-7,8-dicarbanido-undecaborate (-), ANC, using two different conjugation methods, glutaraldehyde crosslinking and coupling via Traut's reagent. The hEGF-ANC conjugates were astatine labelled using the Chloramine-T method. The stability of the labelled compounds was tested by incubation at 37°C. Results: The conjugates were astatinated using the Chloramine-T method in high yield. The best labelling yields were obtained by the glutaraldehyde conjugate with an average yield of 70.5±2.2%. In vitro stability tests indicated that the introduced label was as stable as hEGF labelled with astatobenzoate. Conclusion: Conjugation of nido-carboranes to peptides creates binding sites for direct astatine labelling that can be performed in mild conditions (p 7.2) with high labelling yields.
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| 7. |
- Timmer, Stefan A J, et al.
(författare)
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Reappraisal of a single-tissue compartment model for estimation of myocardial oxygen consumption by [11C]acetate PET : an alternative to conventional monoexponential curve fitting
- 2011
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Ingår i: Nuclear medicine communications. - 0143-3636 .- 1473-5628. ; 32:1, s. 59-62
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Tidskriftsartikel (refereegranskat)abstract
- Background:Myocardial washout kinetics of carbon-11 labelled acetate ([11C]acetate) by positron emission tomography (PET) closely correlate with myocardial oxygen consumption (MVO2). Analysis of the tissue time activity curve by conventional monoexponential curve fitting, however, does not account for spillover effects and recirculating 11C activity. In theory, a compartment model considering variations of the arterial input function and metabolic 11C contamination, could improve consistency of MVO2 estimations. The objective of the study was to investigate this hypothesis.Methods: Nineteen healthy volunteers were studied under resting conditions with [11C]acetate PET. Time activity curves were analysed by automated monoexponential curve fitting and a single-tissue compartment model to obtain Kmono and k2, as noninvasive indices of MVO2. Subsequently, Kmono and k2 were related to the rate-pressure product, as an indirect marker of MVO2.Results:The rate-pressure product was significantly correlated to Kmono (r=0.46, P=0.047) and k2 (r=0.75, P<0.001).Conclusion:The results of this study suggest that a single-tissue compartment model yields more accurate noninvasive estimates of MVO2 by the use of [11C]acetate PET in humans, in comparison with monoexponential curve fitting.
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| 8. |
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| 9. |
- Wang, Ellen, et al.
(författare)
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Automated functional characterization of radiolabeled antibodies : a time-resolved approach
- 2014
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Ingår i: Nuclear medicine communications. - 0143-3636 .- 1473-5628. ; 35:7, s. 767-776
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Tidskriftsartikel (refereegranskat)abstract
- Background The number of radiolabeled monoclonal antibodies (mAbs) used for medical imaging and cancer therapy is increasing. The required chemical modification for attaching a radioactive label and all associated treatment may lead to a damaged mAb subpopulation. This paper describes a novel method, concentration through kinetics (CTK), for rapid assessment of the concentration of immunoreactive mAb and the specific radioactivity, based on monitoring binding kinetics. Methods The interaction of radiolabeled mAb with either the antigen or a general mAb binder such as Protein A was monitored in real time using the instrument LigandTracer. As the curvature of the binding trace has a distinct shape based on the interaction kinetics and concentration of the functional mAb, the immunoreactive mAb concentration could be calculated through reverse kinetic fitting of the binding curves, using software developed for this project. The specific activity, describing the degree of radioactive labeling, was determined through the use of calibrated signal intensities. Results The performance of the CTK assay was evaluated on the basis of various mAb-based interaction systems and assay formats, and it was shown that the assay can provide accurate and repeatable results for immunoreactive concentration and specific activity, with both accuracy and relative SD values below 15%. Conclusion By applying reverse kinetics on real-time binding traces it is possible to estimate the functional concentration and specific activity of radiolabeled mAb. The CTK assay may in the future be included as a complement to current quality assessment methods of radiolabeled mAbs.
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| 10. |
- Wolfensberger, Saskia P, et al.
(författare)
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Quantification of the neurokinin 1 receptor ligand [¹¹C]R116301
- 2011
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Ingår i: Nuclear medicine communications. - 0143-3636 .- 1473-5628. ; 32:10, s. 896-902
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE:Neurokinin 1 (NK1) receptors have been implicated in depression, anxiety, and pain perception. Recently, it was shown that, in the human brain, a specific NK1 receptor-related signal was obtained with the novel radioligand, [¹¹C]R116301, using positron emission tomography. The purpose of this study was to evaluate various methods for quantifying specific [¹¹C]R116301 binding.METHODS:Two dynamic 90-min [¹¹C]R116301 scans, separated by 5 h, were performed in 11 healthy volunteers. In three patients, the second scan was performed after an oral blocking dose of 125 mg of aprepitant, whereas in the other eight, no intervention was performed (test-retest). Whole striatum was used as the tissue of interest, as it has the highest density of NK1 receptors. Cerebellum was used as the reference tissue.RESULTS:Reference tissue models were stable with the simplified reference tissue model (SRTM) performing best. Average (± standard deviation) SRTM-derived mean nondisplaceable binding potential (BP(ND)) of all (first) baseline scans was 0.64±0.31 (n=11), which reduced to -0.01±0.03 (n=3) after aprepitant administration. Test-retest results showed low variability (14.0±10.7%) and excellent reliability, as indicated by the intraclass correlation coefficient (0.93). The ratio of standardized uptake values of striatum and cerebellum minus 1, an approximation of BP(ND), showed very low variability (6.2±3.1%) with excellent reliability (intraclass correlation coefficient=0.98), and correlated well with SRTM-derived BP(ND) (R²=0.96).CONCLUSION:SRTM is the model of choice for quantifying [¹¹C]R116301 binding. Semiquantitative tissue ratios hold promise for routine clinical applications.
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