Nuclear medicine

The researches find that the a two-step surface modification methodology to radiolabel small extracellular vesicles (SEVs) with 64CuCl2 for PET/MRI imaging. The modification did not change or damage the morphology, surface receptor proteins and internal RNA content. Radiolabeled SEVs  detect in organs with low accumulation such as the brain (0.4-0.5% ID/g) and their brain location determine by MRI. SEVs are nanovesicles, with sizes ranging between 30 and 200nm, secreted by cells.

PET/MRI imaging

They contain biomolecules (mRNA, miRNA, proteins and lipids) important for cell-cell communication. There is an increasing interest in using these SEVs for diagnostic (e.g. early detection of cancer, myocardial infarction; stroke) but also for regenerative medicine applications. In the latter case; SEVs isolate from mesenchymal stromal cells (MSCs) umbilical cord blood as well as other cell/tissues have been tested for the treatment of ischemic diseases including stroke; myocardial infarction and chronic wounds.

In addition, SEVs have been engineered to act as delivery systems of siRNA and miRNAs to interfere with tissue biology. Therefore, methods to track SEVs in vivo and follow their biodistribution are very important to fully evaluate their regenerative potential. Fluorescence, luminescence; magnetic resonance imaging (MRI) computed tomography14 and single-photon emission computed tomography (SPECT)   imaging techniques have been used to monitor in vivo SEVs.

Cell-cell communication

Fluorescence and luminescence techniques are relatively easy to operate; readily accessible in research labs and can provide spatiotemporal distribution of SEVs; however, they do not offer high sensitivity and absolute quantification. An alternative to fluorescence/luminescence techniques is MRI which offers anatomic information. In this case, SEVs are typically labelle with super paramagnetic iron oxide nanoparticles with sizes between 5 and 150 nm.

Unfortunately, MRI does not have enough sensitivity for the low concentration (normally 10 µM to 10 mM contrast agent was needed for MRI whereas picomolar concentration of radiotracer was enough for PET or SPECT imaging)18 of SEVs typically accumulated in tissue. Computed tomography requires the labelling of SEVs with inorganic nanoparticles which may accumulate in tissues.

SPECT/CT offers sensitivity

Alternatively, SPECT/CT offers sensitivity; however; the acquisition and quantification of the images raises some technical issues and the stability and bioactivity of the labelled SEVs have not been demonstrated. PET imaging is a very interesting alternative to SPECT for SEV tracking as PET is superior to SPECT regarding sensitivity (approximately 2 to 3 orders of magnitude)19 and provides quantitative images. During the submission of this study, a PET/MRI imaging technique for SEV tracking has been reported.

The study used 124I, with a half-life over 4 days, which is react covalently with the tyrosine aminoacids of proteins in the SEV membrane. PET imaging is combine with computed tomography (CT) to include anatomical details. Despite the significant progresses, the effect of iodine in the properties of EVs (e.g. intravesicle content, cell internalization, SEV bioactivity).