CD24-targeted fluorescence imaging in patient-derived xenograft models of high-grade serous ovarian carcinoma.
Adult
Aged
Aged, 80 and over
Animals
Antibodies, Monoclonal
/ chemistry
CD24 Antigen
/ metabolism
Carboplatin
/ therapeutic use
Cell Line, Tumor
Cystadenocarcinoma, Serous
/ diagnostic imaging
Female
Fluorescent Dyes
/ chemistry
Humans
Mice
Middle Aged
Molecular Imaging
/ methods
Neoplasm Grading
Neoplasm Transplantation
Optical Imaging
Ovarian Neoplasms
/ diagnostic imaging
Paclitaxel
/ therapeutic use
Sensitivity and Specificity
Biomarker
CD24
Fluorescence imaging
HGSOC
High-grade serous ovarian cancer
Optical imaging
PDX
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
30
10
2019
revised:
02
04
2020
accepted:
21
04
2020
pubmed:
27
5
2020
medline:
13
4
2021
entrez:
27
5
2020
Statut:
ppublish
Résumé
The survival rate of patients with advanced high-grade serous ovarian carcinoma (HGSOC) remains disappointing. Clinically translatable orthotopic cell line xenograft models and patient-derived xenografts (PDXs) may aid the implementation of more personalised treatment approaches. Although orthotopic PDX reflecting heterogeneous molecular subtypes are considered the most relevant preclinical models, their use in therapeutic development is limited by lack of appropriate imaging modalities. We developed novel orthotopic xenograft and PDX models for HGSOC, and applied a near-infrared fluorescently labelled monoclonal antibody targeting the cell surface antigen CD24 for non-invasive molecular imaging of epithelial ovarian cancer. CD24-Alexa Fluor 680 fluorescence imaging was compared to bioluminescence imaging in three orthotopic cell line xenograft models of ovarian cancer (OV-90 Application of the near-infrared probe, CD24-AF680, enabled both spatio-temporal visualisation of tumour development, and longitudinal therapy monitoring of orthotopic xenografts. Notably, CD24-AF680 facilitated imaging of multiple PDX models representing different histological subtypes of the disease. The combined implementation of CD24-AF680 and orthotopic PDX models creates a state-of-the-art preclinical platform which will impact the identification and validation of new targeted therapies, fluorescence image-guided surgery, and ultimately the outcome for HGSOC patients. This study was supported by the H2020 program MSCA-ITN [675743], Helse Vest RHF, and Helse Bergen HF [911809, 911852, 912171, 240222, HV1269], as well as by The Norwegian Cancer Society [182735], and The Research Council of Norway through its Centers of excellence funding scheme [223250, 262652].
Sections du résumé
BACKGROUND
BACKGROUND
The survival rate of patients with advanced high-grade serous ovarian carcinoma (HGSOC) remains disappointing. Clinically translatable orthotopic cell line xenograft models and patient-derived xenografts (PDXs) may aid the implementation of more personalised treatment approaches. Although orthotopic PDX reflecting heterogeneous molecular subtypes are considered the most relevant preclinical models, their use in therapeutic development is limited by lack of appropriate imaging modalities.
METHODS
METHODS
We developed novel orthotopic xenograft and PDX models for HGSOC, and applied a near-infrared fluorescently labelled monoclonal antibody targeting the cell surface antigen CD24 for non-invasive molecular imaging of epithelial ovarian cancer. CD24-Alexa Fluor 680 fluorescence imaging was compared to bioluminescence imaging in three orthotopic cell line xenograft models of ovarian cancer (OV-90
FINDINGS
RESULTS
Application of the near-infrared probe, CD24-AF680, enabled both spatio-temporal visualisation of tumour development, and longitudinal therapy monitoring of orthotopic xenografts. Notably, CD24-AF680 facilitated imaging of multiple PDX models representing different histological subtypes of the disease.
INTERPRETATION
CONCLUSIONS
The combined implementation of CD24-AF680 and orthotopic PDX models creates a state-of-the-art preclinical platform which will impact the identification and validation of new targeted therapies, fluorescence image-guided surgery, and ultimately the outcome for HGSOC patients.
FUNDING
BACKGROUND
This study was supported by the H2020 program MSCA-ITN [675743], Helse Vest RHF, and Helse Bergen HF [911809, 911852, 912171, 240222, HV1269], as well as by The Norwegian Cancer Society [182735], and The Research Council of Norway through its Centers of excellence funding scheme [223250, 262652].
Identifiants
pubmed: 32454401
pii: S2352-3964(20)30157-2
doi: 10.1016/j.ebiom.2020.102782
pmc: PMC7248428
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
CD24 Antigen
0
CD24 protein, human
0
Fluorescent Dyes
0
Carboplatin
BG3F62OND5
Paclitaxel
P88XT4IS4D
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102782Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no conflicts of interest.
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