Page 15 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Patient and drug selection becomes increasingly important in nowadays 1 societal discussions about affordability of so-called “expensive targeted drugs”
(13). Therefore, it is important to answer the following questions:
• Which patient (or subgroup of patients) will benefit from the drug?
• Which drug has high potential (safety and efficacy) for further development?
For antibody-based therapy, target engagement in the tumor is considered a requirement for efficacy, while target engagement in normal tissues considered unfavorable (e.g. for development of antibody-drug conjugates).
A reliable biomarker of target engagement could increase efficacy and reduce unnecessary toxicity and costs. In addition, detection of subgroups of patients benefitting from treatment would omit the need for large randomized clinical trials with heterogeneous patient populations. Intelligent trial design including a biomarker could shorten the time from early clinical development to approval of antibody-based therapy.
Antibody imaging with immuno-PET
Antibody imaging can provide a potential biomarker to predict toxicity and efficacy. Advantages of an imaging biomarker are that it is non-invasive and provides whole body information about normal tissues and tumors. Positron emission tomography (PET) can be used as an imaging modality to obtain functional information on a mAb, after its labeling with a positron emitting radionuclide. A radiolabeled mAb is administered intravenously and subsequently PET-CT scans are acquired to visualize and quantify the distribution over the body. This technique is referred to as antibody-PET or more common as immuno- PET.
Intact mAbs require a relative long period of time (days) to reach the target and accumulate. Therefore, zirconium-89 with a half-life of 78.4 hours is a suitable long-lived positron emitter for immuno-PET (14). Radiolabeling methods were developed and reagents made worldwide available to allow production of stable 89Zr-labeled mAbs according to Good Manufacturing Practice (GMP) for clinical use (15, 16).
In daily clinical practice, 18F-fluoro-2-deoxy-glucose (FDG) is the most widely used radiotracer for PET. Increased uptake of 18F-FDG corresponds with increased glucose metabolism (17). As high glucose uptake is a hallmark of
Introduction
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