Zr-89-Immuno-Positron Emission Tomography in Oncology: State-of the-Art Zr-89 Radiochemistry

Immuno-positron emission tomography (immuno-PET) with Zr-89-labeled antibodies has shown great potential in cancer imaging. It can provide important information about the pharmacokinetics and tumor-targeting properties of monoclonal antibodies and may help in anticipating on toxicity. Furthermore, it allows accurate dose planning for individualized radioimmunotherapy and may aid in patient selection and early-response monitoring for targeted therapies. The most commonly used chelator for Zr-89 is desferrioxamine (DFO). Preclinical studies have shown that DFO is not an ideal chelator because the Zr-89 DFO complex is partly unstable in vivo, which results in the release of Zr-89 from the chelator and the subsequent accumulation of Zr-89 in bone. This bone accumulation interferes with accurate interpretation and quantification of bone uptake on PET images. Therefore, there is a need for novel chelators that allow more stable complexation of Zr-89. In this Review, we will describe the most recent developments in Zr-89 radiochemistry, including novel chelators and site-specific conjugation methods.