Page 91 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Initial clinical trials with 89Zr-immuno-PET in oncology
for toxicity. However, so far no clinical studies reported that 89Zr-immuno-PET predicted toxicity of mAb or mAb conjugate treatment, or guided drug development in early stages.
Prediction of response to treatment for mAbs, is based on the assumption
that the drug can only be effective if the target antigen is reached. Although this is
no guarantee for efficacy, as therapy failure may occur due to inadequate dosing of
the mAb or intrinsic resistance mechanisms. To improve prediction of efficacy of
treatment, confirmation of tumor targeting of the drug can be combined with
early response assessment. This combined approach may be able to predict whether
adequate tumor targeting is followed by sufficient cytotoxicity. Clinical application 4 of molecular imaging to guide individualized treatment may ideally consist of the
following 3-step approach:
1. Tumor detection and staging of the disease with conventional imaging (e.g. FDG-PET/diagnostic CT)
2. Assessment of tumor targeting of the drug with molecular imaging (e.g. 89Zr-immuno-PET)
3. Early response assessment on treatment with conventional imaging (e.g. FDG-PET/diagnostic CT)
So far, the ZEPHIR study is the only study utilizing this 3-step approach, using an optimized 89Zr-mAb dose for imaging, and a visual classification for tumor uptake (25). This study reported that molecular imaging combined with early response assessment is able to predict response to treatment with T-DM1 in patients with HER2-positive breast cancer, opening avenues to cost-effectiveness studies and individualized treatment protocols. Still, this promising result can possibly benefit from improving criteria of positive uptake by quantitative analysis.
Currently, no standardized scale for visual scoring of 89Zr-immuno-PET is available, as opposed to scoring FDG-PET/CT scans by the Deauville criteria (47). Imaging procedures, including data analysis and measurements of tumor uptake should be standardized and validated in order to use 89Zr-immuno-PET in clinical practice. As an example, problems with partial volume effects should be solved. Ideally, by linking imaging data with corresponding clinical outcome of a large set of patients, a criterion for positive tumor uptake can be defined.
Overall, these initial clinical trials have provided indications of the potential of 89Zr-immuno-PET as an imaging biomarker to assess target expression, as well as tumor targeting. The first results supporting application of molecular imaging
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