Page 101 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Noise-induced variability of 89Zr-immuno-PET
INTRODUCTION
Antibody imaging is of interest to improve efficacy and limit toxicity of antibody
treatment by providing a predictive imaging biomarker for antibody uptake. Zr- 89-immuno-PET can be used for in vivo quantification of antibody biodistribution
and tumor uptake (1,2). Knowledge about measurement variability is required for
clinical application. Usually, a test-retest study is performed for novel tracers to
assess repeatability. However, for Zr-89-immuno-PET, repeatability is unknown.
A classical test-retest study design with two tracer injections is challenging in case
of Zr-89-immuno-PET because of the long half-life of Zr-89 (78.4 hours). This
requires more than 10 days between two injections to have less than 10% of the radioactivity due to the first injection remaining in the body. In addition, radiation
exposure is significant (0.5 mSv/MBq) (3). To date, most clinical PET studies using Zr-89-labeled mAbs are performed with an injected dose of 37 MBq, resulting in 5 an effective dose of 18.5 mSv. We hypothesize that the relatively low signal to noise
ratio for Zr-89-immuno-PET acquisition (due to the low injected dose and low positron abundance of Zr-89) results in a considerable source of measurement variability.
The primary objective of this study was therefore to assess noise induced variability of quantitative uptake measures derived from Zr-89-immuno-PET for an injected dose of 37 MBq using count-reduced images.
For this purpose, previously acquired clinical datasets can be used to assess noise induced variability at 50% of the original injected dose. Raw PET data (list mode data) can be split in two equal parts (Figure 1). The split list mode data can be reconstructed into two count-reduced images (4). Each of the two count- reduced images is considered to be a count statistically independent estimate of an image that would have been obtained with 50% of the original injected dose for the same scan time. For example, an original image acquired with an injected dose of 74 MBq results in two count-reduced images representing an injected dose of 37 MBq (denoted as 37MBq74inj). The count reduced images are not independent with respect to other factors such as procedural variations or scanner drift.
In addition, we hypothesize that noise induced variability is independent of the investigated mAb, therefore the secondary objective was to investigate clinical datasets with three different Zr-89-labeled mAbs. Finally, the tertiary objective was to assess noise induced variability of Zr-89-immuno-PET for an injected dose of 18 MBq. This is the lowest injected dose used in clinical Zr-89-immuno-PET
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