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

Background: (89)Zirconium-immuno-positron emission tomography (Zr-89-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 Zr-89-labeled antibody disposition in the tumor. Literature values for trastuzumab kinetics were used to provide an example. Results: Zr-89-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 Zr-89-trastuzumab, uptake can discriminate between immunohistochemistry score (IHC) 0 versus 1-2-3. Conclusion: The example for Zr-89-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.

Automated summary

The study investigated the relationship between antibody tumor uptake and target concentration using mathematical modeling of Zr-89-labeled antibody disposition, with trastuzumab kinetics serving as an example. Results showed that Zr-89-trastuzumab uptake initially increases with increasing target concentration before leveling off, influenced by the total administered mass dose of the antibody. The findings suggest the potential of Zr-89-trastuzumab uptake in assessing target expression, while also highlighting the importance of defining clinical target positivity and considering the administered mass dose to avoid false-positive results.