Potential and pitfalls of ⁸⁹Zr-immuno-PET to assess target status: ⁸⁹Zr-trastuzumab as an example

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.