Page 207 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

FUTURE PERSPECTIVES
In this thesis, we found that 89Zr-immuno-PET is safe and feasible. An important advantage of 89Zr-immuno-PET is that whole-body information can be obtained non-invasively and quantitatively. Recently, progress has been made to facilitate improved chemical procedures (11) and by providing recommendations to obtain quantitative accuracy and harmonized image quality for 89Zr-immuno-PET in a multicenter setting (12, 13). 89Zr-immuno-PET studies have been collected in an online accessible warehouse of molecular imaging data with the aim to increase and exchange knowledge on whole body drug distribution (14). The first 89Zr- immuno-PET studies with immune checkpoint inhibitors, antibody drug conjugates and bispecific antibodies show promising results (15-17).
Disadvantages of 89Zr-immuno-PET are the radiation exposure, scan time required and the complexity of logistics. The studies on measurement variability of 89Zr-immuno-PET for tumor quantification described in this thesis indicate that noise is a significant contribution. We studied validity of 89Zr-immuno-PET and observed correlations between tumor uptake on 89Zr-immuno-PET and underlying biology. However, potential false-positive findings indicate the need for quantification. Therefore, we developed methods using dose-dependency and multiple time point scans to assess target-mediated uptake for normal tissues as a crucial step.
Future studies should focus on the following aspects: 1. Improvement of precision by reduction of noise
New technical developments to optimize sensitivity are expected to result in shorter scan time, higher resolution and increased precision. In 2018, the first total-body PET/CT scanner was introduced (18,19). Opposed to current PET/CT scanners that use a ring that allows only 10-15% of the body within the field of view at one time, the total-body PET/CT scanner uses detector rings that cover the entire body. This system allows almost maximal detection of radiation emitted, resulting in increased signal-to-noise ratio in the images (18). This can become a game changer in the application of 89Zr-immuno-PET. Shorter scan time/reduction of administered radioactivity will allow to perform test- retest studies to assess repeatability of 89Zr-immuno-PET. Repeatability studies are usually performed for technical validation. However, until
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Summary and discussion
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