Background: 89Zirconium-immuno-positron emission tomography (89Zr-immuno-PET) is used for assessment of target status to guide antibody-based therapy. We aim to determine the relation between antibody tumor uptake and target concentration to improve future study design and interpretation. Methods: The relation between tumor uptake and target concentration was predicted by mathematical modeling of 89Zr-labeled antibody disposition in the tumor. Literature values for trastuzumab kinetics were used to provide an example. Results: 89Zr-trastuzumab uptake initially increases with increasing target concentration, until it levels off to a constant value. This is determined by the total administered mass dose of trastuzumab. For a commonly used imaging dose of 50 mg 89Zr-trastuzumab, uptake can discriminate between immunohistochemistry score (IHC) 0 versus 1–2–3. Conclusion: The example for 89Zr-trastuzumab illustrates the potential to assess target expression. The pitfall of false-positive findings depends on the cut-off to define clinical target positivity (i.e., IHC 3) and the administered mass dose.
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Huisman, M. C., Menke-van der Houven van Oordt, C. W., Zijlstra, J. M., Hoekstra, O. S., Boellaard, R., van Dongen, G. A. M. S., … Jauw, Y. W. S. (2021). Potential and pitfalls of 89Zr-immuno-PET to assess target status: 89Zr-trastuzumab as an example. EJNMMI Research, 11(1). https://doi.org/10.1186/s13550-021-00813-7
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