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Development and validation of the Normalized Organoid Growth Rate (NOGR) metric in brightfield imaging-based assays
Christophe Deben1, Edgar Cardenas De La Hoz2, Felicia Rodrigues Fortes3
1Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, Wilrijk, Belgium. christophe.deben@uantwerpen.be.
Abstract:
This study focuses on refining growth-rate-based drug response metrics for patient-derived tumor organoid screening using brightfield live-cell imaging. Traditional metrics like Normalized Growth Rate Inhibition (GR) and Normalized Drug Response (NDR) have been used to assess organoid responses to anticancer treatments but face limitations in accurately quantifying cytostatic and cytotoxic effects across varying growth rates. Here, we introduce the Normalized Organoid Growth Rate (NOGR) metric, specifically developed for brightfield imaging-based assays. A label-free image analysis model was applied to segment organoids precisely, track their growth rates over time, and classify viable and dead organoids. Testing eleven phenotypically distinct pancreatic cancer organoid models with five chemotherapeutics demonstrates that the NOGR metric more effectively captures cytostatic and cytotoxic drug effects compared to existing methods. This approach enhances the biological relevance of drug sensitivity assessments on organoids and offers a valuable tool for advancing personalized cancer treatment strategies.
Insights
This study introduces a new metric, Normalized Organoid Growth Rate (NOGR), for analyzing patient-derived tumor organoids. NOGR improves the assessment of anticancer drug effects, enhancing personalized cancer treatment strategies.
Area of Science:
- Oncology
- Biotechnology
- Drug Discovery
Background:
- Patient-derived tumor organoids are crucial for personalized cancer therapy.
- Existing drug response metrics (GR, NDR) have limitations in quantifying cytostatic and cytotoxic effects.
- Brightfield live-cell imaging offers a label-free method for organoid analysis.
Purpose of the Study:
- To develop and validate a novel growth-rate-based metric for organoid drug screening.
- To improve the accuracy of assessing anticancer drug efficacy using brightfield imaging.
- To enhance the biological relevance of organoid drug sensitivity assessments.
Main Methods:
- Developed the Normalized Organoid Growth Rate (NOGR) metric for brightfield imaging.
- Utilized a label-free image analysis model for organoid segmentation and tracking.
- Assessed organoid viability and growth rates over time.
Main Results:
- The NOGR metric demonstrated superior performance in capturing cytostatic and cytotoxic drug effects.
- NOGR effectively evaluated drug responses across eleven distinct pancreatic cancer organoid models.
- Compared to traditional metrics, NOGR provided more biologically relevant drug sensitivity data.
Conclusions:
- The NOGR metric offers a more accurate and biologically relevant approach to organoid drug screening.
- This novel metric can significantly advance personalized cancer treatment strategies.
- NOGR is a valuable tool for researchers in oncology and drug development.
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