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Article: Harmonization of brain PET images in multi-center PET studies using Hoffman phantom scan.

Shekari, Mahnaz / Verwer, Eline E / Yaqub, Maqsood / Daamen, Marcel / Buckley, Christopher / Frisoni, Giovanni B / Visser, Pieter Jelle / Farrar, Gill / Barkhof, Frederik / Gispert, Juan Domingo / Boellaard, Ronald

EJNMMI physics

2023 Volume 10, Issue 1, Page(s) 68

Abstract: Background: Image harmonization has been proposed to minimize heterogeneity in brain PET scans acquired in multi-center studies. However, standard validated methods and software tools are lacking. Here, we assessed the performance of a framework for the ...

Abstract	Background: Image harmonization has been proposed to minimize heterogeneity in brain PET scans acquired in multi-center studies. However, standard validated methods and software tools are lacking. Here, we assessed the performance of a framework for the harmonization of brain PET scans in a multi-center European clinical trial. Method: Hoffman 3D brain phantoms were acquired in 28 PET systems and reconstructed using site-specific settings. Full Width at Half Maximum (FWHM) of the Effective Image Resolution (EIR) and harmonization kernels were estimated for each scan. The target EIR was selected as the coarsest EIR in the imaging network. Using "Hoffman 3D brain Analysis tool," indicators of image quality were calculated before and after the harmonization: The Coefficient of Variance (COV%), Gray Matter Recovery Coefficient (GMRC), Contrast, Cold-Spot RC, and left-to-right GMRC ratio. A COV% ≤ 15% and Contrast ≥ 2.2 were set as acceptance criteria. The procedure was repeated to achieve a 6-mm target EIR in a subset of scans. The method's robustness against typical dose-calibrator-based errors was assessed. Results: The EIR across systems ranged from 3.3 to 8.1 mm, and an EIR of 8 mm was selected as the target resolution. After harmonization, all scans met acceptable image quality criteria, while only 13 (39.4%) did before. The harmonization procedure resulted in lower inter-system variability indicators: Mean ± SD COV% (from 16.97 ± 6.03 to 7.86 ± 1.47%), GMRC Inter-Quartile Range (0.040-0.012), and Contrast SD (0.14-0.05). Similar results were obtained with a 6-mm FWHM target EIR. Errors of ± 10% in the DRO activity resulted in differences below 1 mm in the estimated EIR. Conclusion: Harmonizing the EIR of brain PET scans significantly reduced image quality variability while minimally affecting quantitative accuracy. This method can be used prospectively for harmonizing scans to target sharper resolutions and is robust against dose-calibrator errors. Comparable image quality is attainable in brain PET multi-center studies while maintaining quantitative accuracy.
Language	English
Publishing date	2023-10-31
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2768912-8
ISSN	2197-7364
ISSN	2197-7364
DOI	10.1186/s40658-023-00588-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Reply: Simplified Methods for Quantification of 18F-Fluoromethylcholine Uptake: Is SUVAUC,PP Actually an SUV?

Verwer, Eline E / Lammertsma, Adriaan A / Boellaard, Ronald

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2015 Volume 56, Issue 11, Page(s) 1806–1807

MeSH term(s)	Choline/analogs & derivatives ; Humans ; Male ; Prostatic Neoplasms/diagnostic imaging ; Radionuclide Imaging ; Radiopharmaceuticals
Chemical Substances	Radiopharmaceuticals ; Choline (N91BDP6H0X)
Language	English
Publishing date	2015-11
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.115.164087
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Article: Positron emission tomography to assess hypoxia and perfusion in lung cancer.

Verwer, Eline E / Boellaard, Ronald / van der Veldt, Astrid Am

World journal of clinical oncology

2014 Volume 5, Issue 5, Page(s) 824–844

Abstract: In lung cancer, tumor hypoxia is a characteristic feature, which is associated with a poor prognosis and resistance to both radiation therapy and chemotherapy. As the development of tumor hypoxia is associated with decreased perfusion, perfusion ... ...

Abstract	In lung cancer, tumor hypoxia is a characteristic feature, which is associated with a poor prognosis and resistance to both radiation therapy and chemotherapy. As the development of tumor hypoxia is associated with decreased perfusion, perfusion measurements provide more insight into the relation between hypoxia and perfusion in malignant tumors. Positron emission tomography (PET) is a highly sensitive nuclear imaging technique that is suited for non-invasive in vivo monitoring of dynamic processes including hypoxia and its associated parameter perfusion. The PET technique enables quantitative assessment of hypoxia and perfusion in tumors. To this end, consecutive PET scans can be performed in one scan session. Using different hypoxia tracers, PET imaging may provide insight into the prognostic significance of hypoxia and perfusion in lung cancer. In addition, PET studies may play an important role in various stages of personalized medicine, as these may help to select patients for specific treatments including radiation therapy, hypoxia modifying therapies, and antiangiogenic strategies. In addition, specific PET tracers can be applied for monitoring therapy. The present review provides an overview of the clinical applications of PET to measure hypoxia and perfusion in lung cancer. Available PET tracers and their characteristics as well as the applications of combined hypoxia and perfusion PET imaging are discussed.
Language	English
Publishing date	2014-12-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2587357-X
ISSN	2218-4333
ISSN	2218-4333
DOI	10.5306/wjco.v5.i5.824
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Article: Quantitative implications of the updated EARL 2019 PET-CT performance standards.

Kaalep, Andres / Burggraaff, Coreline N / Pieplenbosch, Simone / Verwer, Eline E / Sera, Terez / Zijlstra, Josee / Hoekstra, Otto S / Oprea-Lager, Daniela E / Boellaard, Ronald

EJNMMI physics

2019 Volume 6, Issue 1, Page(s) 28

Abstract: Purpose: Recently, updated EARL specifications (EARL2) have been developed and announced. This study aims at investigating the impact of the EARL2 specifications on the quantitative reads of clinical PET-CT studies and testing a method to enable the use ...

Abstract	Purpose: Recently, updated EARL specifications (EARL2) have been developed and announced. This study aims at investigating the impact of the EARL2 specifications on the quantitative reads of clinical PET-CT studies and testing a method to enable the use of the EARL2 standards whilst still generating quantitative reads compliant with current EARL standards (EARL1). Methods: Thirteen non-small cell lung cancer (NSCLC) and seventeen lymphoma PET-CT studies were used to derive four image datasets-the first dataset complying with EARL1 specifications and the second reconstructed using parameters as described in EARL2. For the third (EARL2F6) and fourth (EARL2F7) dataset in EARL2, respectively, 6 mm and 7 mm Gaussian post-filtering was applied. We compared the results of quantitative metrics (MATV, SUVmax, SUVpeak, SUVmean, TLG, and tumor-to-liver and tumor-to-blood pool ratios) obtained with these 4 datasets in 55 suspected malignant lesions using three commonly used segmentation/volume of interest (VOI) methods (MAX41, A50P, SUV4). Results: We found that with EARL2 MAX41 VOI method, MATV decreases by 22%, TLG remains unchanged and SUV values increase by 23-30% depending on the specific metric used. The EARL2F7 dataset produced quantitative metrics best aligning with EARL1, with no significant differences between most of the datasets (p>0.05). Different VOI methods performed similarly with regard to SUV metrics but differences in MATV as well as TLG were observed. No significant difference between NSCLC and lymphoma cancer types was observed. Conclusions: Application of EARL2 standards can result in higher SUVs, reduced MATV and slightly changed TLG values relative to EARL1. Applying a Gaussian filter to PET images reconstructed using EARL2 parameters successfully yielded EARL1 compliant data.
Language	English
Publishing date	2019-12-26
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2768912-8
ISSN	2197-7364
ISSN	2197-7364
DOI	10.1186/s40658-019-0257-8
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Article ; Online: [

Marquié, Marta / Agüero, Cinthya / Amaral, Ana C / Villarejo-Galende, Alberto / Ramanan, Prianca / Chong, Michael Siao Tick / Sáez-Calveras, Nil / Bennett, Rachel E / Verwer, Eline E / Kim, Sally Ji Who / Dhaynaut, Maeva / Alvarez, Victor E / Johnson, Keith A / McKee, Ann C / Frosch, Matthew P / Gómez-Isla, Teresa

Acta neuropathologica communications

2019 Volume 7, Issue 1, Page(s) 164

Abstract: Introduction: Chronic traumatic encephalopathy (CTE) is a tauopathy associated to repetitive head trauma. There are no validated in vivo biomarkers of CTE and a definite diagnosis can only be made at autopsy. Recent studies have shown that positron ... ...

Abstract	Introduction: Chronic traumatic encephalopathy (CTE) is a tauopathy associated to repetitive head trauma. There are no validated in vivo biomarkers of CTE and a definite diagnosis can only be made at autopsy. Recent studies have shown that positron emission tomography (PET) tracer AV-1451 (Flortaucipir) exhibits high binding affinity for paired helical filament (PHF)-tau aggregates in Alzheimer (AD) brains but relatively low affinity for tau lesions in other tauopathies like temporal lobal degeneration (FTLD)-tau, progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). Little is known, however, about the binding profile of this ligand to the tau-containing lesions of CTE. Objective: To study the binding properties of [ Methods: We performed [ Results: Despite the presence of abundant tau aggregates in multiple regions in all CTE brains, only faint or no [ Conclusion: AV-1451 may have limited utility for in vivo selective and reliable detection of tau aggregates in CTE. The existence of disease-specific tau conformations may likely explain the differential binding affinity of this tracer for tau lesions in different tauopathies.
MeSH term(s)	Aged ; Aged, 80 and over ; Brain/metabolism ; Brain/pathology ; Carbolines ; Chronic Traumatic Encephalopathy/complications ; Chronic Traumatic Encephalopathy/metabolism ; Chronic Traumatic Encephalopathy/pathology ; Female ; Humans ; Male ; Middle Aged ; Positron-Emission Tomography ; Tauopathies/complications ; Tauopathies/metabolism ; Tauopathies/pathology ; tau Proteins/analysis ; tau Proteins/metabolism
Chemical Substances	Carbolines ; MAPT protein, human ; tau Proteins ; 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole (J09QS3Z3WB)
Language	English
Publishing date	2019-10-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2715589-4
ISSN	2051-5960 ; 2051-5960
ISSN (online)	2051-5960
ISSN	2051-5960
DOI	10.1186/s40478-019-0808-1
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Article ; Online: [F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging.

Marquié, Marta / Siao Tick Chong, Michael / Antón-Fernández, Alejandro / Verwer, Eline E / Sáez-Calveras, Nil / Meltzer, Avery C / Ramanan, Prianca / Amaral, Ana C / Gonzalez, Jose / Normandin, Marc D / Frosch, Matthew P / Gómez-Isla, Teresa

Acta neuropathologica

2017 Volume 134, Issue 4, Page(s) 619–628

Abstract: F-18]-AV-1451, a PET tracer specifically developed to detect brain neurofibrillary tau pathology, has the potential to facilitate accurate diagnosis of Alzheimer's disease (AD), staging of brain tau burden and monitoring disease progression. Recent PET ... ...

Abstract	[F-18]-AV-1451, a PET tracer specifically developed to detect brain neurofibrillary tau pathology, has the potential to facilitate accurate diagnosis of Alzheimer's disease (AD), staging of brain tau burden and monitoring disease progression. Recent PET studies show that patients with mild cognitive impairment and AD dementia exhibit significantly higher in vivo [F-18]-AV-1451 retention than cognitively normal controls. Importantly, PET patterns of [F-18]-AV-1451 correlate well with disease severity and seem to match the predicted topographic Braak staging of neurofibrillary tangles (NFTs) in AD, although this awaits confirmation. We studied the correlation of autoradiographic binding patterns of [F-18]-AV-1451 and the stereotypical spatiotemporal pattern of progression of NFTs using legacy postmortem brain samples representing different Braak NFT stages (I-VI). We performed [F-18]-AV-1451 phosphor-screen autoradiography and quantitative tau measurements (stereologically based NFT counts and biochemical analysis of tau pathology) in three brain regions (entorhinal cortex, superior temporal sulcus and visual cortex) in a total of 22 cases: low Braak (I-II, n = 6), intermediate Braak (III-IV, n = 7) and high Braak (V-VI, n = 9). Strong and selective [F-18]-AV-1451 binding was detected in all tangle-containing regions matching precisely the observed pattern of PHF-tau immunostaining across the different Braak stages. As expected, no signal was detected in the white matter or other non-tangle containing regions. Quantification of [F-18]-AV-1451 binding was very significantly correlated with the number of NFTs present in each brain region and with the total tau and phospho-tau content as reported by Western blot and ELISA. [F-18]-AV-1451 is a promising biomarker for in vivo quantification of brain tau burden in AD. Neuroimaging-pathologic studies conducted on postmortem material from individuals imaged while alive are now needed to confirm these observations.
MeSH term(s)	Aged ; Aged, 80 and over ; Autoradiography ; Blotting, Western ; Brain/diagnostic imaging ; Brain/metabolism ; Brain/pathology ; Carbolines ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neurofibrillary Tangles/metabolism ; Neurofibrillary Tangles/pathology ; Phosphorylation ; Plaque, Amyloid/metabolism ; Plaque, Amyloid/pathology ; Radiopharmaceuticals ; Severity of Illness Index ; tau Proteins/metabolism
Chemical Substances	Carbolines ; MAPT protein, human ; Radiopharmaceuticals ; tau Proteins ; 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole (J09QS3Z3WB)
Language	English
Publishing date	2017-06-13
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1079-0
ISSN	1432-0533 ; 0001-6322
ISSN (online)	1432-0533
ISSN	0001-6322
DOI	10.1007/s00401-017-1740-8
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Article ; Online: Pharmacokinetic Evaluation of the Tau PET Radiotracer

Wooten, Dustin W / Guehl, Nicolas J / Verwer, Eline E / Shoup, Timothy M / Yokell, Daniel L / Zubcevik, Nevena / Vasdev, Neil / Zafonte, Ross D / Johnson, Keith A / El Fakhri, Georges / Normandin, Marc D

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2016 Volume 58, Issue 3, Page(s) 484–491

Abstract: ... ...

Abstract	18
MeSH term(s)	Adult ; Aged ; Brain/metabolism ; Carbolines/blood ; Carbolines/pharmacokinetics ; Computer Simulation ; Humans ; Metabolic Clearance Rate ; Middle Aged ; Models, Biological ; Molecular Imaging/methods ; Organ Specificity ; Positron-Emission Tomography/methods ; Radiopharmaceuticals/blood ; Radiopharmaceuticals/pharmacokinetics ; Reproducibility of Results ; Sensitivity and Specificity ; Tissue Distribution ; tau Proteins/metabolism
Chemical Substances	Carbolines ; MAPT protein, human ; Radiopharmaceuticals ; tau Proteins ; 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole (J09QS3Z3WB)
Language	English
Publishing date	2016-09-22
Publishing country	United States
Document type	Evaluation Study ; Journal Article
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.115.170910
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Article ; Online: Multiparametric Analysis of the Relationship Between Tumor Hypoxia and Perfusion with ¹⁸F-Fluoroazomycin Arabinoside and ¹⁵O-H₂O PET.

Iqbal, Ramsha / Kramer, Gem M / Verwer, Eline E / Huisman, Marc C / de Langen, Adrianus J / Bahce, Idris / van Velden, Floris H P / Windhorst, Albert D / Lammertsma, Adriaan A / Hoekstra, Otto S / Boellaard, Ronald

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2016 Volume 57, Issue 4, Page(s) 530–535

Abstract: Unlabelled: (18)F-fluoroazomycin arabinoside ((18)F-FAZA) is a PET tracer of tumor hypoxia. However, as hypoxia often is associated with decreased perfusion, the delivery of (18)F-FAZA may be compromised, potentially disturbing the association between ... ...

Abstract	Unlabelled: (18)F-fluoroazomycin arabinoside ((18)F-FAZA) is a PET tracer of tumor hypoxia. However, as hypoxia often is associated with decreased perfusion, the delivery of (18)F-FAZA may be compromised, potentially disturbing the association between tissue hypoxia and (18)F-FAZA uptake. The aim of this study was to gain insight into the relationship between tumor perfusion and (18)F-FAZA uptake. Methods: Ten patients diagnosed with advanced non-small cell lung cancer underwent subsequent dynamic (15)O-H2O and (18)F-FAZA PET scans with arterial sampling. Parametric images of both (15)O-H2O-derived perfusion (tumor blood flow [TBF]) and volume of distribution (V(T)) of (18)F-FAZA were generated. Next, multiparametric classification was performed using lesional and global thresholds. Voxels were classified as low or high TBF and (18)F-FAZA V(T), respectively. Finally, by combining these initial classifications, voxels were allocated to 4 categories: lowTBF-lowV(T), lowTBF-highV(T), highTBF-lowV(T), and highTBF-highV(T). Results: A total of 13 malignant lesions were identified in the 10 patients. The TBF and (18)F-FAZA V(T) values (average ± SD) across all lesions were 0.45 ± 0.20 mL·cm(-3)·min(-1) and 0.94 ± 0.31 mL·cm(-3), respectively. The averages of all lesional median values for TBF and (18)F-FAZA V(T) were 0.37 ± 0.15 mL·cm(-3)·min(-1) and 0.85 ± 0.18 mL·cm(-3), respectively. Multiparametric analysis showed that classified voxels were clustered rather than randomly distributed. Several intralesion areas were identified where (18)F-FAZA V(T) was inversely related to TBF. On the other hand, there were also distinct areas where TBF as well as (18)F-FAZA V(T) were decreased or increased. Conclusion: The present data indicate that spatial variation of (18)F-FAZA uptake is not necessarily inversely related to TBF. This suggests that decreased TBF may result in flow-limited delivery of (18)F-FAZA. Areas with both high (18)F-FAZA uptake and high TBF values suggest that high (18)F-FAZA uptake, possibly suggesting hypoxia, may occur despite high TBF values. In conclusion, multiparametric evaluation of the spatial distributions of both TBF and (18)F-FAZA uptake may be helpful for understanding the (18)F-FAZA signal.
MeSH term(s)	Aged ; Carcinoma, Non-Small-Cell Lung/diagnostic imaging ; Cluster Analysis ; Female ; Humans ; Hypoxia/metabolism ; Lung Neoplasms/diagnostic imaging ; Male ; Middle Aged ; Neoplasms/blood supply ; Neoplasms/diagnostic imaging ; Neoplasms/metabolism ; Nitroimidazoles/pharmacokinetics ; Oxygen Radioisotopes ; Positron-Emission Tomography ; Radiopharmaceuticals/pharmacokinetics ; Regional Blood Flow ; Water/chemistry
Chemical Substances	Nitroimidazoles ; Oxygen Radioisotopes ; Radiopharmaceuticals ; Water (059QF0KO0R) ; fluoroazomycin arabinoside (1QR3UU6P48)
Language	English
Publishing date	2016-04
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.115.166579
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Article ; Online: Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson's case.

Marquié, Marta / Verwer, Eline E / Meltzer, Avery C / Kim, Sally Ji Who / Agüero, Cinthya / Gonzalez, Jose / Makaretz, Sara J / Siao Tick Chong, Michael / Ramanan, Prianca / Amaral, Ana C / Normandin, Marc D / Vanderburg, Charles R / Gomperts, Stephen N / Johnson, Keith A / Frosch, Matthew P / Gómez-Isla, Teresa

Acta neuropathologica communications

2017 Volume 5, Issue 1, Page(s) 75

Abstract: F-18]-AV-1451 is a novel positron emission tomography (PET) tracer with high affinity to neurofibrillary tau pathology in Alzheimer's disease (AD). PET studies have shown increased tracer retention in patients clinically diagnosed with dementia of AD ... ...

Abstract	[F-18]-AV-1451 is a novel positron emission tomography (PET) tracer with high affinity to neurofibrillary tau pathology in Alzheimer's disease (AD). PET studies have shown increased tracer retention in patients clinically diagnosed with dementia of AD type and mild cognitive impairment in regions that are known to contain tau lesions. In vivo uptake has also consistently been observed in midbrain, basal ganglia and choroid plexus in elderly individuals regardless of their clinical diagnosis, including clinically normal whose brains are not expected to harbor tau pathology in those areas. We and others have shown that [F-18]-AV-1451 exhibits off-target binding to neuromelanin, melanin and blood products on postmortem material; and this is important for the correct interpretation of PET images. In the present study, we further investigated [F-18]-AV-1451 off-target binding in the first autopsy-confirmed Parkinson's disease (PD) subject who underwent antemortem PET imaging. The PET scan showed elevated [F-18]-AV-1451 retention predominantly in inferior temporal cortex, basal ganglia, midbrain and choroid plexus. Neuropathologic examination confirmed the PD diagnosis. Phosphor screen and high resolution autoradiography failed to show detectable [F-18]-AV-1451 binding in multiple brain regions examined with the exception of neuromelanin-containing neurons in the substantia nigra, leptomeningeal melanocytes adjacent to ventricles and midbrain, and microhemorrhages in the occipital cortex (all reflecting off-target binding), in addition to incidental age-related neurofibrillary tangles in the entorhinal cortex. Additional legacy postmortem brain samples containing basal ganglia, choroid plexus, and parenchymal hemorrhages from 20 subjects with various neuropathologic diagnoses were also included in the autoradiography experiments to better understand what [F-18]-AV-1451 in vivo positivity in those regions means. No detectable [F-18]-AV-1451 autoradiographic binding was present in the basal ganglia of the PD case or any of the other subjects. Off-target binding in postmortem choroid plexus samples was only observed in subjects harboring leptomeningeal melanocytes within the choroidal stroma. Off-target binding to parenchymal hemorrhages was noticed in postmortem material from subjects with cerebral amyloid angiopathy. The imaging-postmortem correlation analysis in this PD case reinforces the notion that [F-18]-AV-1451 has strong affinity for neurofibrillary tau pathology but also exhibits off-target binding to neuromelanin, melanin and blood components. The robust off-target in vivo retention in basal ganglia and choroid plexus, in the absence of tau deposits, meningeal melanocytes or any other identifiable binding substrate by autoradiography in the PD case reported here, also suggests that the PET signal in those regions may be influenced, at least in part, by biological or technical factors that occur in vivo and are not captured by autoradiography.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Autoradiography ; Brain/diagnostic imaging ; Brain/metabolism ; Brain Mapping ; Carbolines ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/diagnostic imaging ; Parkinson Disease/metabolism ; Parkinson Disease/pathology ; Positron-Emission Tomography ; Radiopharmaceuticals
Chemical Substances	Carbolines ; Radiopharmaceuticals ; 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole (J09QS3Z3WB)
Language	English
Publishing date	2017-10-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2715589-4
ISSN	2051-5960 ; 2051-5960
ISSN (online)	2051-5960
ISSN	2051-5960
DOI	10.1186/s40478-017-0482-0
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Article ; Online: Quantification of 18F-fluorocholine kinetics in patients with prostate cancer.

Verwer, Eline E / Oprea-Lager, Daniela E / van den Eertwegh, Alfons J M / van Moorselaar, Reindert J A / Windhorst, Albert D / Schwarte, Lothar A / Hendrikse, N Harry / Schuit, Robert C / Hoekstra, Otto S / Lammertsma, Adriaan A / Boellaard, Ronald

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2015 Volume 56, Issue 3, Page(s) 365–371

Abstract: Unlabelled: Choline kinase is upregulated in prostate cancer, resulting in increased (18)F-fluoromethylcholine uptake. This study used pharmacokinetic modeling to validate the use of simplified methods for quantification of (18)F-fluoromethylcholine ... ...

Abstract	Unlabelled: Choline kinase is upregulated in prostate cancer, resulting in increased (18)F-fluoromethylcholine uptake. This study used pharmacokinetic modeling to validate the use of simplified methods for quantification of (18)F-fluoromethylcholine uptake in a routine clinical setting. Methods: Forty-minute dynamic PET/CT scans were acquired after injection of 204 ± 9 MBq of (18)F-fluoromethylcholine, from 8 patients with histologically proven metastasized prostate cancer. Plasma input functions were obtained using continuous arterial blood-sampling as well as using image-derived methods. Manual arterial blood samples were used for calibration and correction for plasma-to-blood ratio and metabolites. Time-activity curves were derived from volumes of interest in all visually detectable lymph node metastases. (18)F-fluoromethylcholine kinetics were studied by nonlinear regression fitting of several single- and 2-tissue plasma input models to the time-activity curves. Model selection was based on the Akaike information criterion and measures of robustness. In addition, the performance of several simplified methods, such as standardized uptake value (SUV), was assessed. Results: Best fits were obtained using an irreversible compartment model with blood volume parameter. Parent fractions were 0.12 ± 0.4 after 20 min, necessitating individual metabolite corrections. Correspondence between venous and arterial parent fractions was low as determined by the intraclass correlation coefficient (0.61). Results for image-derived input functions that were obtained from volumes of interest in blood-pool structures distant from tissues of high (18)F-fluoromethylcholine uptake yielded good correlation to those for the blood-sampling input functions (R(2) = 0.83). SUV showed poor correlation to parameters derived from full quantitative kinetic analysis (R(2) < 0.34). In contrast, lesion activity concentration normalized to the integral of the blood activity concentration over time (SUVAUC) showed good correlation (R(2) = 0.92 for metabolite-corrected plasma; 0.65 for whole-blood activity concentrations). Conclusion: SUV cannot be used to quantify (18)F-fluoromethylcholine uptake. A clinical compromise could be SUVAUC derived from 2 consecutive static PET scans, one centered on a large blood-pool structure during 0-30 min after injection to obtain the blood activity concentrations and the other a whole-body scan at 30 min after injection to obtain lymph node activity concentrations.
MeSH term(s)	Aged ; Calibration ; Choline/analogs & derivatives ; Choline/chemistry ; Humans ; Kinetics ; Lymph Nodes/diagnostic imaging ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Metastasis ; Positron-Emission Tomography ; Prostatectomy ; Prostatic Neoplasms/diagnostic imaging ; Radiopharmaceuticals/chemistry ; Regression Analysis ; Time Factors ; Tomography, X-Ray Computed
Chemical Substances	Radiopharmaceuticals ; fluorocholine ; fluoromethylcholine ; Choline (N91BDP6H0X)
Language	English
Publishing date	2015-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.114.148007
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 114: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 328: Show issues

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