Optimal imaging time points considering accuracy and precision of Patlak linearization for 89Zr-immuno-PET: a simulation study

Abstract Purpose Zirconium-89-immuno-positron emission tomography (89Zr-immuno-PET) has enabled visualization of zirconium-89 labelled monoclonal antibody (89Zr-mAb) uptake in organs and tumors in vivo. Patlak linearization of 89Zr-immuno-PET quantification data allows for separation of reversible a...

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Main Authors: Jessica E. Wijngaarden, Marc C. Huisman, Johanna E. E. Pouw, C. Willemien Menke-van der Houven van Oordt, Yvonne W. S. Jauw, Ronald Boellaard
Format: Article
Language:English
Published: SpringerOpen 2022-09-01
Series:EJNMMI Research
Subjects:
Online Access:https://doi.org/10.1186/s13550-022-00927-6
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author Jessica E. Wijngaarden
Marc C. Huisman
Johanna E. E. Pouw
C. Willemien Menke-van der Houven van Oordt
Yvonne W. S. Jauw
Ronald Boellaard
author_facet Jessica E. Wijngaarden
Marc C. Huisman
Johanna E. E. Pouw
C. Willemien Menke-van der Houven van Oordt
Yvonne W. S. Jauw
Ronald Boellaard
author_sort Jessica E. Wijngaarden
collection DOAJ
description Abstract Purpose Zirconium-89-immuno-positron emission tomography (89Zr-immuno-PET) has enabled visualization of zirconium-89 labelled monoclonal antibody (89Zr-mAb) uptake in organs and tumors in vivo. Patlak linearization of 89Zr-immuno-PET quantification data allows for separation of reversible and irreversible uptake, by combining multiple blood samples and PET images at different days. As one can obtain only a limited number of blood samples and scans per patient, choosing the optimal time points is important. Tissue activity concentration curves were simulated to evaluate the effect of imaging time points on Patlak results, considering different time points, input functions, noise levels and levels of reversible and irreversible uptake. Methods Based on 89Zr-mAb input functions and reference values for reversible (V T ) and irreversible (K i ) uptake from literature, multiple tissue activity curves were simulated. Three different 89Zr-mAb input functions, five time points between 24 and 192 h p.i., noise levels of 5, 10 and 15%, and three reference K i and V T values were considered. Simulated K i and V T were calculated (Patlak linearization) for a thousand repetitions. Accuracy and precision of Patlak linearization were evaluated by comparing simulated K i and V T with reference values. Results Simulations showed that K i is always underestimated. Inclusion of time point 24 h p.i. reduced bias and variability in V T , and slightly reduced bias and variability in K i , as compared to combinations of three later time points. After inclusion of 24 h p.i., minimal differences were found in bias and variability between different combinations of later imaging time points, despite different input functions, noise levels and reference values. Conclusion Inclusion of a blood sample and PET scan at 24 h p.i. improves accuracy and precision of Patlak results for 89Zr-immuno-PET; the exact timing of the two later time points is not critical.
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spelling doaj.art-f7e591d6ed574f1a8604194122efd8632022-12-22T03:13:00ZengSpringerOpenEJNMMI Research2191-219X2022-09-011211910.1186/s13550-022-00927-6Optimal imaging time points considering accuracy and precision of Patlak linearization for 89Zr-immuno-PET: a simulation studyJessica E. Wijngaarden0Marc C. Huisman1Johanna E. E. Pouw2C. Willemien Menke-van der Houven van Oordt3Yvonne W. S. Jauw4Ronald Boellaard5Department of Radiology and Nuclear Medicine, Amsterdam UMC location Vrije Universiteit AmsterdamDepartment of Radiology and Nuclear Medicine, Amsterdam UMC location Vrije Universiteit AmsterdamDepartment of Medical Oncology, Amsterdam UMC location Vrije Universiteit AmsterdamDepartment of Medical Oncology, Amsterdam UMC location Vrije Universiteit AmsterdamDepartment of Radiology and Nuclear Medicine, Amsterdam UMC location Vrije Universiteit AmsterdamDepartment of Radiology and Nuclear Medicine, Amsterdam UMC location Vrije Universiteit AmsterdamAbstract Purpose Zirconium-89-immuno-positron emission tomography (89Zr-immuno-PET) has enabled visualization of zirconium-89 labelled monoclonal antibody (89Zr-mAb) uptake in organs and tumors in vivo. Patlak linearization of 89Zr-immuno-PET quantification data allows for separation of reversible and irreversible uptake, by combining multiple blood samples and PET images at different days. As one can obtain only a limited number of blood samples and scans per patient, choosing the optimal time points is important. Tissue activity concentration curves were simulated to evaluate the effect of imaging time points on Patlak results, considering different time points, input functions, noise levels and levels of reversible and irreversible uptake. Methods Based on 89Zr-mAb input functions and reference values for reversible (V T ) and irreversible (K i ) uptake from literature, multiple tissue activity curves were simulated. Three different 89Zr-mAb input functions, five time points between 24 and 192 h p.i., noise levels of 5, 10 and 15%, and three reference K i and V T values were considered. Simulated K i and V T were calculated (Patlak linearization) for a thousand repetitions. Accuracy and precision of Patlak linearization were evaluated by comparing simulated K i and V T with reference values. Results Simulations showed that K i is always underestimated. Inclusion of time point 24 h p.i. reduced bias and variability in V T , and slightly reduced bias and variability in K i , as compared to combinations of three later time points. After inclusion of 24 h p.i., minimal differences were found in bias and variability between different combinations of later imaging time points, despite different input functions, noise levels and reference values. Conclusion Inclusion of a blood sample and PET scan at 24 h p.i. improves accuracy and precision of Patlak results for 89Zr-immuno-PET; the exact timing of the two later time points is not critical.https://doi.org/10.1186/s13550-022-00927-689Zr-immuno-PETPatlak linearizationMonoclonal antibodyMolecular imaging
spellingShingle Jessica E. Wijngaarden
Marc C. Huisman
Johanna E. E. Pouw
C. Willemien Menke-van der Houven van Oordt
Yvonne W. S. Jauw
Ronald Boellaard
Optimal imaging time points considering accuracy and precision of Patlak linearization for 89Zr-immuno-PET: a simulation study
EJNMMI Research
89Zr-immuno-PET
Patlak linearization
Monoclonal antibody
Molecular imaging
title Optimal imaging time points considering accuracy and precision of Patlak linearization for 89Zr-immuno-PET: a simulation study
title_full Optimal imaging time points considering accuracy and precision of Patlak linearization for 89Zr-immuno-PET: a simulation study
title_fullStr Optimal imaging time points considering accuracy and precision of Patlak linearization for 89Zr-immuno-PET: a simulation study
title_full_unstemmed Optimal imaging time points considering accuracy and precision of Patlak linearization for 89Zr-immuno-PET: a simulation study
title_short Optimal imaging time points considering accuracy and precision of Patlak linearization for 89Zr-immuno-PET: a simulation study
title_sort optimal imaging time points considering accuracy and precision of patlak linearization for 89zr immuno pet a simulation study
topic 89Zr-immuno-PET
Patlak linearization
Monoclonal antibody
Molecular imaging
url https://doi.org/10.1186/s13550-022-00927-6
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