TY - JOUR
T1 - Optimal imaging time points considering accuracy and precision of Patlak linearization for 89Zr-immuno-PET
T2 - a simulation study
AU - Wijngaarden, Jessica E.
AU - Huisman, Marc C.
AU - Pouw, Johanna E. E.
AU - Menke-van der Houven van Oordt, C. Willemien
AU - Jauw, Yvonne W. S.
AU - Boellaard, Ronald
N1 - Funding Information: This work has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 831514 (Immune-Image). The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. Publisher Copyright: © 2022, The Author(s).
PY - 2022
Y1 - 2022
N2 - 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 (VT) and irreversible (Ki) 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 Ki and VT values were considered. Simulated Ki and VT were calculated (Patlak linearization) for a thousand repetitions. Accuracy and precision of Patlak linearization were evaluated by comparing simulated Ki and VT with reference values. Results: Simulations showed that Ki is always underestimated. Inclusion of time point 24 h p.i. reduced bias and variability in VT, and slightly reduced bias and variability in Ki, 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.
AB - 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 (VT) and irreversible (Ki) 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 Ki and VT values were considered. Simulated Ki and VT were calculated (Patlak linearization) for a thousand repetitions. Accuracy and precision of Patlak linearization were evaluated by comparing simulated Ki and VT with reference values. Results: Simulations showed that Ki is always underestimated. Inclusion of time point 24 h p.i. reduced bias and variability in VT, and slightly reduced bias and variability in Ki, 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.
KW - Molecular imaging
KW - Monoclonal antibody
KW - Patlak linearization
KW - Zr-immuno-PET
UR - http://www.scopus.com/inward/record.url?scp=85137974128&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s13550-022-00927-6
DO - https://doi.org/10.1186/s13550-022-00927-6
M3 - Article
C2 - 36065038
SN - 2191-219X
VL - 12
JO - EJNMMI Research
JF - EJNMMI Research
IS - 1
M1 - 54
ER -