Radiolabelling of Extracellular Vesicles for PET and SPECT imaging

Extracellular vesicles (EVs) such as exosomes and microvesicles have gained recent attention as potential biomarkers of disease as well as nanomedicinal tools, but their behaviour in vivo remains mostly unexplored. In order to gain knowledge of their in vivo biodistribution it is important to develop imaging tools that allow us to track EVs over time and at the whole-body level. Radionuclide-based imaging (PET and SPECT) have properties that allow us to do so efficiently, mostly due to their high sensitivity, imaging signal tissue penetration, and accurate quantification. Furthermore, they can be easily translated from animals to humans.

Researchers from King’s College London summarise and discuss the different studies that have used PET or SPECT to study the behaviour of EVs in vivo. With a focus on the different radiolabelling methods used, they also discuss the advantages and disadvantages of each one, and the challenges of imaging EVs due to their variable stability and heterogeneity.

Schematic representation of different EV radiolabelling methods

A) Surface radiolabelling: radionuclide can be incorporated into the EV membrane directly or via a chelator. B) Intraluminal radiolabelling: ionophores allow radionuclides to be transported across the lipid membrane where they can be trapped as their lipophilicity changes or bind to metal chelating biomolecules.