Patient-derived cancer organoid tracking with wide-field one-photon redox imaging to assess treatment response.
autofluorescence
cancer organoid
drug screening
image analysis
redox imaging
tracking
Journal
Journal of biomedical optics
ISSN: 1560-2281
Titre abrégé: J Biomed Opt
Pays: United States
ID NLM: 9605853
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
11
12
2020
accepted:
24
02
2021
entrez:
23
3
2021
pubmed:
24
3
2021
medline:
25
9
2021
Statut:
ppublish
Résumé
Accessible tools are needed for rapid, non-destructive imaging of patient-derived cancer organoid (PCO) treatment response to accelerate drug discovery and streamline treatment planning for individual patients. To segment and track individual PCOs with wide-field one-photon redox imaging to extract morphological and metabolic variables of treatment response. Redox imaging of the endogenous fluorophores, nicotinamide dinucleotide (NADH), nicotinamide dinucleotide phosphate (NADPH), and flavin adenine dinucleotide (FAD), was used to monitor the metabolic state and morphology of PCOs. Redox imaging was performed on a wide-field one-photon epifluorescence microscope to evaluate drug response in two colorectal PCO lines. An automated image analysis framework was developed to track PCOs across multiple time points over 48 h. Variables quantified for each PCO captured metabolic and morphological response to drug treatment, including the optical redox ratio (ORR) and organoid area. The ORR (NAD(P)H/(FAD + NAD(P)H)) was independent of PCO morphology pretreatment. Drugs that induced cell death decreased the ORR and growth rate compared to control. Multivariate analysis of redox and morphology variables identified distinct PCO subpopulations. Single-organoid tracking improved sensitivity to drug treatment compared to pooled organoid analysis. Wide-field one-photon redox imaging can monitor metabolic and morphological changes on a single organoid-level, providing an accessible, non-destructive tool to screen drugs in patient-matched samples.
Identifiants
pubmed: 33754540
pii: JBO-200400R
doi: 10.1117/1.JBO.26.3.036005
pmc: PMC7983069
doi:
Substances chimiques
NAD
0U46U6E8UK
Flavin-Adenine Dinucleotide
146-14-5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : R01 CA185747
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA205101
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA211082
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA226526
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014520
Pays : United States
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