Journal
BIOCONJUGATE CHEMISTRY
Volume 28, Issue 9, Pages 2211-2223Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.7b00325
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Funding
- Innovative Medicines Initiatives 2 Joint Undertaking [116106]
- European Union
- Netherlands Organisation for Scientific Research (NWO) [91617039]
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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.
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