Page 185 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Towards 89Zr-immuno-PET to measure target engagement of antibodies
For tissues without target expression, the entire irreversible component is due to non-target mediated mAb degradation (and subsequent residualizing of 89Zr). Endosomal mAb degradation is a non-specific catabolic mechanism for all intact IgG molecules. Per day, 6.3% of the intravascular IgG pool is catabolized (23). Therefore, the whole body catabolic rate was estimated at 7.8 mL∙h-1, using a reference total plasma volume (22). The contribution of individual tissues (experimentally determined in mice) was 6%, 30%, 1.3% and 2.8% for kidney, liver, lung and spleen, respectively (11). These values were used to predict the irreversible component for tissues without target expression.
To compare the 89Zr-immuno-PET derived value for the net rate of irreversible uptake in μL×g-1×h-1 to the catabolic rate in mL×h-1, Ki was multiplied by tissue volume (22).
Predicted values for VT and Ki, including literature values used, are presented in Supplemental Table 1.
Statistical Analysis
Values for VT and Ki are presented per tissue, and per 89Zr-mAb. Median values
and interquartile ranges were reported due to the small sample size per group.
In addition, a baseline value was obtained by combining the n values for tissues
without target expression. For example, no target expression in the kidney was
reported for CD20, EGFR and HER2 (Table 1) (20). Therefore, 89Zr-antiCD20, 89Zr-antiEGFR and 89Zr-antiHER data were combined to determine the
baseline value for VT and Ki, for kidney tissue without target expression.
Baseline values for liver consisted of 89Zr-antiCD20. For lung, data on 89Zr-
antiCD20, 89Zr-antiEGFR and 89Zr-antiPSMA were combined to obtain the
baseline value. For spleen, the baseline value consisted of 89Zr-antiEGFR and 89Zr-antiHER2. 9
The Wilcoxon signed rank test was used to determine whether the n values for VT for tissues without target expression (baseline values) differed from the predicted value. A p-value <0.05 was considered statistically significant. Statistical tests were performed in GraphPad Prism, version 6.02.
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