Open AccessPET Imaging of Small Extracellular Vesicles via [89Zr]Zr(oxinate)4 Direct Radiolabeling
Author(s) -
Azalea Khan,
Francis Man,
Farid N. Faruqu,
Jana Kim,
Fahad Al-Salemee,
Amaia Carrascal-Miniño,
Alessia Volpe,
Revadee LiamOr,
Paul Simpson,
Gilbert O. Fruhwirth,
Khuloud T. AlJamal,
Rafael T. M. de Rosales
Publication year - 2022
Publication title -
bioconjugate chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.279
H-Index - 172
eISSN - 1520-4812
pISSN - 1043-1802
DOI - 10.1021/acs.bioconjchem.1c00597
Subject(s) - biodistribution , chemistry , radiosynthesis , in vivo , nanoparticle tracking analysis , positron emission tomography , molecular imaging , drug delivery , preclinical imaging , pet imaging , radiochemistry , imaging agent , microvesicles , biomedical engineering , nanotechnology , biophysics , nuclear medicine , in vitro , biochemistry , materials science , medicine , organic chemistry , biology , gene , microrna , microbiology and biotechnology
Exosomes or small extracellular vesicles (sEVs) are increasingly gaining attention for their potential as drug delivery systems and biomarkers of disease. Therefore, it is important to understand their in vivo biodistribution using imaging techniques that allow tracking over time and at the whole-body level. Positron emission tomography (PET) allows short- and long-term whole-body tracking of radiolabeled compounds in both animals and humans and with excellent quantification properties compared to other nuclear imaging techniques. In this report, we explored the use of [ 89 Zr]Zr(oxinate) 4 (a cell and liposome radiotracer) for direct and intraluminal radiolabeling of several types of sEVs, achieving high radiolabeling yields. The radiosynthesis and radiolabeling protocols were optimized for sEV labeling, avoiding sEV damage, as demonstrated using several characterizations (cryoEM, nanoparticle tracking analysis, dot blot, and flow cytometry) and in vitro techniques. Using pancreatic cancer sEVs (PANC1) in a healthy mouse model, we showed that it is possible to track 89 Zr-labeled sEVs in vivo using PET imaging for at least up to 24 h. We also report differential biodistribution of intact sEVs compared to intentionally heat-damaged sEVs, with significantly reduced spleen uptake for the latter. Therefore, we conclude that 89 Zr-labeled sEVs using this method can reliably be used for in vivo PET tracking and thus allow efficient exploration of their potential as drug delivery systems.