Evidence map›Paper›PMID 39164886›Full record

ArticleMolecular pharmaceutics2024

Investigating the In Vivo Biodistribution of Extracellular Vesicles Isolated from Various Human Cell Sources Using Positron Emission Tomography.

Zachary T Rosenkrans, Anna S Thickens, John A Kink, Eduardo Aluicio-Sarduy, Jonathan W Engle, Peiman Hematti, Reinier Hernandez

Abstract read
In one paragraph

Article in Molecular pharmaceutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed.

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  10. Peripheral nerve repair: innovations and future directions.Journal of translational medicine · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Zachary T RosenkransDepartments of Medical Physics and Radiology, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, Wisconsin 53705, United States.
Anna S ThickensDepartments of Medical Physics and Radiology, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, Wisconsin 53705, United States.
John A KinkDepartment of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, 1685 Highland Avenue, Madison, Wisconsin 53705, United States.
Eduardo Aluicio-SarduyDepartments of Medical Physics and Radiology, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, Wisconsin 53705, United States.
Jonathan W EngleDepartments of Medical Physics and Radiology, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, Wisconsin 53705, United States.ORCID 0000-0002-3399-7228
Peiman HemattiDepartment of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, 1685 Highland Avenue, Madison, Wisconsin 53705, United States.ORCID 0000-0001-5836-4497
Reinier HernandezDepartments of Medical Physics and Radiology, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, Wisconsin 53705, United States.ORCID 0000-0002-0729-2179

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Christian Capitini · 1985 to 2026
$142.6M
U.W. RADIOLOGICAL SCIENCES TRAINING PROGRAMT32CA009206 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Bryan Patrick Bednarz · 1985 to 2026
$12.1M
Exosome educated monocytes for acute radiation syndromeR01HL153721 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI CAPITINI, CHRISTIAN, HEMATTI, PEIMAN · 2021 to 2024
$2.0M
NCI NIH HHS P30 CA014520NCI NIH HHS T32 CA009206NHLBI NIH HHS R01 HL153721
6 · The paper itself

Abstract

Positron emission tomography (PET) is a powerful tool for investigating the in vivo behavior of drug delivery systems. We aimed to assess the biodistribution of extracellular vesicles (EVs), nanosized vesicles secreted by cells isolated from various human cell sources using PET. EVs were isolated from mesenchymal stromal cells (MSCs) (MSC EVs), human macrophages (Mϕ EVs), and a melanoma cell line (A375 EVs) by centrifugation and were conjugated with deferoxamine for radiolabeling with Zr-89. PET using conjugated and radiolabeled EVs evaluated their in vivo biodistribution and tissue tropisms. Our study also investigated differences in mouse models, utilizing immunocompetent and immunocompromised mice and an A375 xenograft tumor model. Lastly, we investigated the impact of different labeling techniques on the observed EV biodistribution, including covalent surface modification and membrane incorporation. PET showed that all tested EVs exhibited extended in vivo circulation and generally low uptake in the liver, spleen, and lungs. However, Mϕ EVs showed high liver uptake, potentially attributable to the intrinsic tissue tropism of these EVs from the surface protein composition. MSC EV biodistribution differed between immunocompetent and immunodeficient mice, with increased spleen uptake observed in the latter. PET using A375 xenografts demonstrated efficient tumor uptake of EVs, but no preferential tissue-specific tropism of A375 EVs was found. Biodistribution differences between labeling techniques showed that surface-conjugated EVs had preferential blood circulation and low liver, spleen, and lung uptake compared to membrane integration. This study demonstrates the potential of EVs as effective drug carriers for various diseases, highlights the importance of selecting appropriate cell sources for EV-based drug delivery, and suggests that EV tropism can be harnessed to optimize therapeutic efficacy. Our findings indicate that the cellular source of EVs, labeling technique, and animal model can influence the observed biodistribution.

Indexed as

Extracellular VesiclesMesenchymal Stem CellsPositron-Emission TomographyAnimalsCell Line, TumorDeferoxamineDrug Delivery SystemsFemaleHumansMacrophagesMelanomaMiceRadioisotopesTissue DistributionXenograft Model Antitumor AssaysZirconiumDeferoxamineRadioisotopesZirconiumZirconium-89biodistributioncancerexosomesextracellular vesiclesimagingpositron emission tomography

Identifiers

PMID39164886
PMCPMC11891749

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.