[89Zr]Zr(oxinate)4 Allows Direct Radiolabelling and PET Imaging of Small Extracellular Vesicles

Khan, Azalea; Man, Francis; Faruqu, Farid N.; Kim, Jana; Al-Salemee, Fahad; Volpe, Alessia; Fruhwirth, Gilbert O.; Al‐Jamal, Khuloud T.; Rosales, Rafael T. M. de

doi:10.26434/chemrxiv.12730463

Cited by 2 publications

(3 citation statements)

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“…In vivo SPECT-CT images using M2-targeted sEVs showed the expected liver and spleen uptake seen with other sEVs, but also interesting uptake in lymph nodes (Fig. 7 C) - a finding that has also been observed with 89 Zr-labelled PANC1 sEVs ( vide infra ) 93 - and lungs. In addition, M2-targeted sEVs showed increased uptake in tumours, as well as significant kidney and bladder signal that the authors assign to excretion of radiolabelled sEVs.…”

Section: Radiolabelling Of Evs Using Spect Radionuclidessupporting

confidence: 66%

“…To date there is one report on intraluminal radiolabelling of sEVs using PET radionuclides 93 . Khan et al exploited the proven cell and liposome radiolabelling capabilities of [ 89 Zr]Zr-oxinate 77 , 111 , 112 , to radiolabel three different cancer cell-derived sEVs with RLYs as high as ca.…”

Section: Radiolabelling Of Evs Using Pet Radionuclidesmentioning

confidence: 99%

“…Ratio of liver:bone uptake (n = 3) and spleen:bone uptake (n = 2) is shown on the right; data given as mean ± SD of the n values and analysed by Student's t-test. Figures taken from Khan et al 93 .…”

Section: Figurementioning

confidence: 99%

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Radiolabelling of Extracellular Vesicles for PET and SPECT imaging

Khan¹,

Rosales²

2021

Nanotheranostics

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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.

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Section: Radiolabelling Of Evs Using Spect Radionuclidessupporting

confidence: 66%

Section: Radiolabelling Of Evs Using Pet Radionuclidesmentioning

confidence: 99%

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Radiolabelling of Extracellular Vesicles for PET and SPECT imaging

Khan¹,

Rosales²

2021

Nanotheranostics

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Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with 89Zr Radioisotope in Mice and Rats

Choi¹,

Kim²,

Kim³

et al. 2022

Pharmaceutics

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For the successful clinical advancement of exosome therapeutics, the biodistribution and pharmacokinetic profile of exogenous exosomes in various animal models must be determined. Compared with fluorescence or bioluminescence imaging, radionuclide imaging confers multiple advantages for the in vivo tracking of biomolecular therapeutics because of its excellent sensitivity for deep tissue imaging and potential for quantitative measurement. Herein, we assessed the quantitative biodistribution and pharmacokinetics of good manufacturing practice-grade therapeutic exosomes labeled with zirconium-89 (89Zr) after systemic intravenous administration in mice and rats. Quantitative biodistribution analysis by positron emission tomography/computed tomography and gamma counting in mice and rats revealed that the total 89Zr signals in the organs were lower in rats than in mice, suggesting a higher excretion rate of exosomes in rats. A prolonged 89Zr signal for up to 7 days in most organs indicated that substantial amounts of exosomes were taken up by the parenchymal cells in those organs, highlighting the therapeutic potential of exosomes for the intracellular delivery of therapeutics. Exosomes were mainly distributed in the liver and to a lesser extent in the spleen, while a moderately distributed in the kidney, lung, stomach, intestine, urinary bladder, brain, and heart. Exosomes were rapidly cleared from the blood circulation, with a rate greater than that of free 89Zr, indicating that exosomes might be rapidly taken up by cells and tissues.

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[89Zr]Zr(oxinate)4 Allows Direct Radiolabelling and PET Imaging of Small Extracellular Vesicles

Abstract: 89Zr]Zr(oxinate)4 allows direct radiolabelling of exosomes/small extracellular vesicles (sEVs) and in vivo PET-CT imaging

Cited by 2 publications

References 24 publications

Radiolabelling of Extracellular Vesicles for PET and SPECT imaging

Radiolabelling of Extracellular Vesicles for PET and SPECT imaging

Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with 89Zr Radioisotope in Mice and Rats

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