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

Immuno-positron emission tomography (immunoPET) with 89 Zr-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 89 Zr is desferrioxamine (DFO). Preclinical studies have shown that DFO is not an ideal chelator because the 89 Zr-DFO complex is partly unstable in vivo, which results in the release of 89 Zr from the chelator and the subsequent accumulation of 89 Zr 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 89 Zr. In this Review, we will describe the most recent developments in 89 Zr radiochemistry, including novel chelators and site-specific conjugation methods.