Page 16 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer
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Chapter 1
malignant cells, 18F-FDG-PET is used for staging and response evaluation for different types of cancer (18, 19). But uptake of 18F-FDG does not provide information on target engagement of mAbs. For this purpose, we aim to develop 89Zr-immuno-PET as a clinical tool to guide antibody-based therapy in cancer.
“It is usually a bad idea to develop a new measurement instrument”
Feasibility (including safety), technical validation, biological/clinical validation and cost effectiveness are required for successful implementation of a novel imaging biomarker in clinical cancer research and in daily clinical practice. Only when no existing measurement instrument is suitable for the specific need, and the purpose is of utmost importance, development of a new measurement instrument can be justified. We consider 89Zr-immuno-PET as a clinical tool to guide antibody-based therapy to meet these criteria, as we described in the previous paragraphs.
Contrary to biospecimen-derived biomarkers (measured from blood or tissue samples), where technical validation usually occurs before biological/clinical validation, these steps are performed in parallel for imaging biomarkers (20).
The following aspects have to be considered to develop 89Zr-immuno-PET as a clinical tool to guide antibody-based therapy in cancer:
1. Feasibility
0 Are 89Zr-labeled mAbs safe to administer?
0 What is the radiation exposure due to 89Zr-immuno-PET? 0 Can 89Zr-immuno-PET visualize tumor uptake?
0 Can tumor uptake and bloodpool activity be quantified
with 89Zr-immuno-PET?
0 Are the ideas and findings of using 89Zr-immuno-PET
relevant and sustainable? 2. Validation
• Technical validation
What is the measurement variability of 89Zr-immuno-PET?
0 What is the measurement variability due to noise (e.g. counting statistics)?
0 What is the interobserver reproducibility of tumor quantification?
• Biological/clinical validation
Is 89Zr-immuno-PET able to measure the underlying biology?
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