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

Abstract

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.

Keywords

• 89Zr-immuno-PET
• Patlak linearization
• Monoclonal antibody
• Molecular imaging