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

ABSTRACT

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.