Potential and pitfalls of 89Zr-immuno-PET to assess target status: 89Zr-trastuzumab as an example
Marc C. Huisman, C. Willemien Menke‐van der Houven van Oordt, Josée M. Zijlstra, Otto S. Hoekstra, Ronald Boellaard, Guus A.M.S. van Dongen, Dhaval K. Shah, Yvonne W. S. Jauw
Abstract
Abstract Background 89 Zirconium-immuno-positron emission tomography ( 89 Zr-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 89 Zr-labeled antibody disposition in the tumor. Literature values for trastuzumab kinetics were used to provide an example. Results 89 Zr-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 89 Zr-trastuzumab, uptake can discriminate between immunohistochemistry score (IHC) 0 versus 1–2–3. Conclusion The example for 89 Zr-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.