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Updated: Jan 10, 2026
Generation of 3D Tumor Spheroids for Drug Evaluation Studies
Published on: February 24, 2023
Design of 3D spheroid models for drug-response studies of HER2-targeted radiopharmaceuticals
Ivan V Zelepukin1, Lisa Fulterer2, Ahmed D Elshazli2
1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, 751 83, Sweden; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
Abstract:
The development of targeted radionuclide- and chemotherapeutics-based drugs requires in vitro models that reflect the structural and molecular complexity of solid tumors. Here, we present a high-throughput 3D cell culture platform for targeted drug response studies. The platform was based on agarose micro-dishes that generate 81 tumor spheroids. The platform was validated across eight human and murine cancer cell lines that overexpress receptors of the HER family. The high spheroid yield supports robust quantitative analysis of binding of radiolabeled compounds, while spheroid trapping in microwells enables medium exchange for precise drug exposure. Therefore, we evaluated targeted radionuclide therapy of EMT-HER2 spheroids using the HER2-specific affibody PEP48937 labelled with terbium-161. We demonstrated both HER2-specific binding to spheroids and receptor-specific therapeutic effects, including reduced spheroid proliferation over time and impaired cell migration. These results highlight the platform potential to accelerate the development of targeted cancer therapeutics for biomedicine.
Insights
A new 3D cell culture platform generates 81 tumor spheroids for high-throughput drug testing. This model accurately assesses targeted radionuclide therapy, showing reduced cancer cell proliferation and migration.
Area of Science:
- Biomedical Engineering
- Oncology
- Drug Development
Background:
- Developing targeted cancer therapeutics requires advanced in vitro models that mimic solid tumor complexity.
- Current models often lack the structural and molecular fidelity needed for precise drug response evaluation.
Purpose of the Study:
- To introduce a high-throughput 3D cell culture platform for evaluating targeted radionuclide and chemotherapy drugs.
- To validate the platform's efficacy using HER2-overexpressing cancer cell lines and targeted radionuclide therapy.
Main Methods:
- Utilized agarose micro-dishes to generate 81 tumor spheroids per platform for high-throughput screening.
- Validated the platform across eight human and murine cancer cell lines overexpressing HER family receptors.
- Assessed targeted radionuclide therapy using a HER2-specific affibody (PEP48937) labeled with terbium-161 on EMT-HER2 spheroids.
Main Results:
- Achieved high spheroid yield, enabling robust quantitative analysis of radiolabeled compound binding.
- Demonstrated HER2-specific binding of the affibody to tumor spheroids.
- Observed receptor-specific therapeutic effects, including reduced spheroid proliferation and impaired cell migration.
Conclusions:
- The developed 3D cell culture platform effectively models solid tumors for targeted drug development.
- The platform facilitates precise drug exposure and quantitative analysis, accelerating therapeutic evaluation.
- This system shows significant potential for advancing targeted cancer therapeutics in biomedicine.
