Wijngaarden Jessica E, Huisman Marc C, Pouw Johanna E E, Menke-van der Houven van Oordt C Willemien, Jauw Yvonne W S, Boellaard Ronald
Department of Radiology and Nuclear Medicine, Amsterdam UMC location Vrije Universiteit Amsterdam, Boelelaan 1117, Amsterdam, The Netherlands.
Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, The Netherlands.
EJNMMI Res. 2022 Sep 5;12(1):54. doi: 10.1186/s13550-022-00927-6.
Zirconium-89-immuno-positron emission tomography (Zr-immuno-PET) has enabled visualization of zirconium-89 labelled monoclonal antibody (Zr-mAb) uptake in organs and tumors in vivo. Patlak linearization of Zr-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 Zr-mAb input functions and reference values for reversible (V) and irreversible (K) uptake from literature, multiple tissue activity curves were simulated. Three different Zr-mAb input functions, five time points between 24 and 192 h p.i., noise levels of 5, 10 and 15%, and three reference K and V values were considered. Simulated K and V were calculated (Patlak linearization) for a thousand repetitions. Accuracy and precision of Patlak linearization were evaluated by comparing simulated K and V with reference values.
Simulations showed that K is always underestimated. Inclusion of time point 24 h p.i. reduced bias and variability in V, and slightly reduced bias and variability in K, 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 Zr-immuno-PET; the exact timing of the two later time points is not critical.
锆 - 89免疫正电子发射断层扫描（Zr - 免疫PET）能够在体内可视化锆 - 89标记的单克隆抗体（Zr - mAb）在器官和肿瘤中的摄取情况。通过在不同日期采集多个血样和PET图像，对Zr - 免疫PET定量数据进行Patlak线性化处理，可分离可逆摄取和不可逆摄取。由于每位患者能够采集的血样和扫描次数有限，因此选择最佳时间点至关重要。考虑不同的时间点、输入函数、噪声水平以及可逆和不可逆摄取水平，模拟组织活性浓度曲线以评估成像时间点对Patlak结果的影响。
基于Zr - mAb输入函数以及文献中可逆摄取（V）和不可逆摄取（K）的参考值，模拟了多条组织活性曲线。考虑了三种不同的Zr - mAb输入函数、接种后24至192小时之间的五个时间点、5%、10%和15%的噪声水平以及三个参考K和V值。对模拟的K和V进行了一千次重复计算（Patlak线性化）。通过将模拟的K和V与参考值进行比较，评估Patlak线性化的准确性和精密度。
模拟结果表明，K始终被低估。与三个较晚时间点的组合相比，纳入接种后24小时的时间点可降低V的偏差和变异性，并略微降低K的偏差和变异性。纳入接种后24小时的时间点后，尽管输入函数、噪声水平和参考值不同，但在较晚成像时间点的不同组合之间，偏差和变异性的差异极小。
在接种后24小时采集血样和进行PET扫描可提高Zr - 免疫PET的Patlak结果的准确性和精密度；后两个时间点的确切时间并不关键。
