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

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.

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.

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.

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.