Zirconium-89 Labeled Antibodies: A New Tool for Molecular Imaging in Cancer Patients

Abstract

Antibody based positron emission tomography (immuno-PET) imaging is of increasing importance to visualize and characterize tumor lesions. Additionally, it can be used to identify patients who may benefit from a particular therapy and monitor the therapy outcome. In recent years the field is focused on 89Zr, a radiometal with near ideal physical and chemical properties for immuno-PET. In this review we will discuss the production of 89Zr, the bioconjugation strategies, and applications in (pre-)clinical studies of 89Zr-based immuno-PET in oncology. To date, 89Zr-based PET imaging has been investigated in a wide variety of cancer-related targets. Moreover, clinical studies have shown the feasibility for 89Zr-based immuno-PET to predict and monitor treatment, which could be used to tailor treatment for the individual patient. Further research should be directed towards the development of standardized and robust conjugation methods and improved chelators to minimize the amount of released Zr4+ from the antibodies. Additionally, further validation of the imaging method is required. The ongoing development of new 89Zr-labeled antibodies directed against novel tumor targets is expected to expand applications of 89Zr-labeled immuno-PET to a valuable method in the medical imaging.

In vivo imaging with antibodies and engineered fragments

“…64 Cu (t 1/2 = 12.7 hr) and 89 Zr (t 1/2 = 78.4 hr) are well-matched for intermediate-sized fragments such as scFvs, diabodies, and minibodies, as well as intact antibodies. Use of 89 Zr has dramatically expanded recently due to its half-life and ease of production; in addition, its positron emissions are lower energy than those of 124 I, improving intrinsic resolution (van de Watering et al, 2014). 89 Zr is usually attached indirectly to an antibody through conjugation of the chelator desferrioxamine (DFO) (van de Watering et al, 2014).…”

Mechanism and non-mechanism based imaging biomarkers for assessing biological response to treatment in non-small cell lung cancer

“…89 Zirconium PET tracer labelling of therapeutic agents (e.g. anti-PD-L1 antibody), has potential to quantify the pharmacokinetics of drug delivery to target [132], as well as to track T-cells for immunotherapy planning and response evaluation [133]. These studies are however investigational and available at specialist centres only.…”

Pharmacokinetics study of Zr-89-labeled melanin nanoparticle in iron-overload mice

“…After water-soluble MP was prepared, 89 Zr was selected as a radiotracer to label MP for investigating the blood half-life and PET imaging properties of MP, due to its moderate half-life (78.4 h) [31]. Traditionally, several chelators have been used for the labeling of 89 Zr to minimize the disassociation of 89 Zr, such as desferoxamine (DFO) and its derivatives [32,33].…”