Characterization of plasma-derived protoporphyrin-IX-positive extracellular vesicles following 5-ALA use in patients with malignant glioma.
EBioMedicine
; 48: 23-35, 2019 Oct.
Article
em En
| MEDLINE
| ID: mdl-31628025
ABSTRACT
BACKGROUND:
Malignant gliomas are rapidly progressive brain tumors with high mortality. Fluorescence guided surgery (FGS) with 5-aminolevulinic acid (5-ALA) provides fluorescent delineation of malignant tissue, which helps achieve maximum safe resection. 5-ALA-based fluorescence is due to preferential accumulation of the fluorophore protoporphyrin-IX (PpIX) in malignant glioma tissue. Additionally, gliomas cells release extracellular vesicles (EVs) which carry biomarkers of disease. Herein, we performed animal and human studies to investigate whether 5-ALA dosed glioma cells, in vitro and in vivo, release PpIX positive EVs in circulation which can be captured and analyzed.METHODS:
We used imaging flow cytometry (IFC) to characterize PpIX-positive EVs released from 5-ALA-dosed glioma cells, glioma-bearing xenograft models, as well as patients with malignant glioma undergoing FGS.FINDINGS:
We first show that glioma cells dosed with 5-ALA release 247-fold higher PpIX positive EVs compared to mock dosed glioma cells. Second, we demonstrate that the plasma of glioma-bearing mice (nâ¯=â¯2) dosed with 5-ALA contain significantly higher levels of circulating PpIX-positive EVs than their pre-dosing background (pâ¯=â¯0.004). Lastly, we also show that the plasma of patients with avidly fluorescent tumors (nâ¯=â¯4) undergoing FGS contain circulating PpIX-positive EVs at levels significantly higher than their pre-dosing background (pâ¯=â¯0.00009) and this rise in signal correlates with enhancing tumor volumes (r 2â¯â¯=â¯0.888).INTERPRETATION:
Our findings highlight the potential of plasma-derived PpIX-positive EV-based diagnostics for malignant gliomas, offering a novel liquid biopsy platform for confirming and monitoring tumor status.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Protoporfirinas
/
Fármacos Fotossensibilizantes
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Vesículas Extracelulares
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Corantes Fluorescentes
/
Glioma
/
Ácidos Levulínicos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adult
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Aged
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Animals
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Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
EBioMedicine
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos