Page 112 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Chapter 5
DISCUSSION
In this study noise induced variability of quantitative uptake measures was assessed for Zr-89-immuno-PET for an injected activity of 37 MBq based on count-reduced images. As expected, a variable increase in RC was observed from D0 to D6 for the manually delineated organs (Table 1). In general, the RC for the manually delineated large organs combined (liver, spleen, kidney, lung and brain) was within 6% at all time points (D0, D3, D6) for 89Zr-anti-CD20 mAb (37MBq74inj). Larger measurement variability was observed for the bone marrow and blood pool VOIs with RC up to 40% at D6 for 89Zr-anti-CD20 (37 MBq74inj). These results are in line with an increase in RC for a lower total activity in the VOI.
For tumor uptake of 89Zr-antiCD20 mAb (37 MBq74inj), the lowest variability was obtained for SUVmean (27%), followed by SUVpeak (35%), while SUVmax (42%) resulted in the highest measurement variability (Table 2). This is as expected, since for a given VOI the mean value takes all voxels into account, in contrast to the peak value (based on a limited number of voxels) and max value (based on a single voxel).
RC for the three Zr-89-mAbs were similar. Therefore, the observed measurement variability is independent of the differences in biodistribution between these three Zr-89-mAbs. These results suggest that similar noise induced variability can be expected for other Zr-89-mAbs, assuming harmonized image quality and a biodistribution within the same range as the Zr-89-mAbs investigated in this study.
With the count-reduced images, noise induced variability for an injected dose of 18 MBq was assessed for all three mAbs. RC for combined organs were up to 12% at all time points (range D0-D6). Tumor RC varied between 20 to 54%, depending on time point and VOI delineation method.
Despite relatively large RC for tumor, blood pool and bone marrow, overall reliability for the three clinical Zr-89-immuno-PET studies previously reported (7-9) was excellent (ICCs approximately 0.9). ICC values are given to show, for these Zr-89-mAbs in their respective patient cohorts, that the measured differences in tumor uptake do exceed the variability induced by noise. ICC values, however, cannot be extrapolated to other Zr-89-mAbs or even different patient cohorts imaged with the same Zr-89-mAb.
As our study provides an assessment of measurement variability due to the signal-to-noise ratio, other sources of measurement error are not represented in
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