Radiolabelling of Extracellular Vesicles for PET and SPECT imaging

Abstract

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. In this review, we 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, we also discuss the advantages and disadvantages of each one, and the challenges of imaging EVs due to their variable stability and heterogeneity.

Nanomaterial Probes for Nuclear Imaging

“…Until 1996, these exosomes were considered debris, but since then, studies have reported the role of exosomes in immune responses such as antigen presentation in immune-modulating activity of B cell-derived vesicles and their potential in immunotherapy [123,[126][127][128]. Extensive research has been done in recent years to gain a deeper understanding of these complex vesicles and their involvement in the cellular system, as well as exploration for potential clinical diagnosis and therapeutics in nanomedicine [125,129,130]. Currently, there are studies to investigate the effects of exosomes on SARS-CoV-2 coronavirus and potential development of exosome-based therapeutic approaches to tackle this deadly virus [131][132][133].…”

“…Currently, there are studies to investigate the effects of exosomes on SARS-CoV-2 coronavirus and potential development of exosome-based therapeutic approaches to tackle this deadly virus [131][132][133]. Evidently, exosomes play a crucial role not only in elimination of unwanted proteins out of the cell but also in other important cellular communications and functions [122,123,126,127,129,[134][135][136].…”

“…Additionally, the involvement of exosomes in cancer progression has also been evidently reported; tumor-derived exosomes (TDEs) are known to be involved in cancer progression [124][125][126]130]. One of the greatest advantages of these exosomes is the ability to cross biological barriers such as the blood-brain barrier easily, and therefore, bypassing potential side effects arising from traditional cell-based therapy [40,125,129,137]. For example, pulmonary embolism that could potentially arise from MSC transplantation in the brain could be avoided [132,133].…”

“…Since exosomes encapsulate many bioactive materials important for paracrine factors, tumor growth, and suppression, these vesicles can serve as biomarkers for diagnosis and prognosis for diseases [124,128,129,138]. Studies have shown that exosome concentrations were found to be higher in the blood of patients with cancer [124,127,128].…”

Diagnostic and Therapeutic Potential of Extracellular Vesicles

“…91,92 Imaging tools commonly used are single-photon emission computed tomography, positron emission tomography, and magnetic resonance imaging. [92][93][94] It should be remembered that the labeling compounds have a longer half-life than EVs and continue to be detected by imaging even after EVs are degraded. 54,95 Bioengineering the EV membranes with inbuilt markers that degrade simultaneously with the EVs will be useful to avoid false-positive findings Table 2.…”