Page 209 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer
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                                Provided that all requirements are met, we envision that 89Zr-immuno-PET can be used in the near future for the following clinical applications:
• “whole-body in-vivo immunohistochemistry” for individualized treatment
• measurement of target engagement in tumor and normal tissues to guide drug development
The latest developments in mAb-based treatment of cancer include many new drugs that have now reached the clinic: antibody-drug conjugates, bispecific antibodies, immune checkpoint inhibitors and chimeric antigen receptor (CAR)-T cells (21). Different mechanisms have been explored to increase the efficacy of traditional mAbs (e.g. use of a toxic payload (ADC) or by triggering the immune system (e.g. activating T-cells to kill the malignant cells). These treatment approaches have in common that their effects are all target-antigen mediated. Therefore, we need to shine a light on whether these drugs reach the disease. This is essential information to better understand their efficacy and toxicity and to learn how to dose appropriately. The timing is crucial to accompany these expensive novel targeted therapies with 89Zr-immuno-PET as biomarker for target engagement, especially as society struggles to find a way towards affordable and accessible healthcare.
CONCLUSION
This thesis describes the development of 89Zr-immuno-PET as a clinical tool to guide antibody-based treatment in cancer. Initial clinical studies of 89Zr-immuno- PET in oncology show feasibility, including safety. Technical validation indicates that multi-center interobserver reproducibility of tumor uptake quantification was excellent, although measurement variability due to noise was substantial. Biological validation studies show that 89Zr-immuno-PET is able to measure the underlying biology (correlation with target expression, dose-dependency and assessment of non-specific uptake). Future work should be aimed at reduction of measurement variability using improved PET-CT scanners, quantification of specific uptake in tumor and clinical validation (e.g. prediction of response to antibody-based treatment). If these requirements are met, 89Zr-immuno-PET can be used as a clinical tool to guide patient and drug selection for antibody-based treatment in cancer.
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Summary and discussion
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