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The potential of targeted radionuclide therapy to treat hypoxic tumor cells
S T M Wenker1, S A M van Lith2, G Tamborino3
1Department of Medical Imaging, Nuclear Medicine, Radboudumc, Nijmegen, the Netherlands; Department of Radiation Oncology, Radiotherapy & Oncoimmunology laboratory, Radboudumc, Nijmegen, the Netherlands.
Abstract:
Tumor hypoxia contributes to cancer progression and therapy resistance. Several strategies have been investigated to relieve tumor hypoxia, of which some were successful. However, their clinical application remains challenging and therefore they are not used in daily clinical practice. Here, we review the potential of targeted radionuclide therapy (TRT) to eradicate hypoxic cancer cells. We present an overview of the published TRT strategies using β--particles, α-particles, and Auger electrons. Altogether, we conclude that α-particle emitting radionuclides are most promising since they can cause DNA double strand breaks independent of oxygen levels. Future directions for research are addressed, including more adequate in vitro and in vivo models to proof the potential of TRT to eliminate hypoxic cancer cells. Furthermore, dosimetry and radiobiology are identified as key to better understand the mechanism of action and dose-response relationships in hypoxic tumor areas. Finally, we can conclude that in order to achieve long-term anti-tumor efficacy, TRT combination treatment strategies may be necessary.
Insights
Targeted radionuclide therapy (TRT) shows promise for treating tumors with low oxygen (hypoxia). Alpha-particle emitting radionuclides are particularly effective against hypoxic cancer cells, offering a new therapeutic avenue.
Area of Science:
- Oncology
- Nuclear Medicine
- Radiotherapy
Background:
- Tumor hypoxia is a key factor in cancer progression and resistance to therapy.
- Current strategies to alleviate tumor hypoxia face clinical application challenges.
- Targeted radionuclide therapy (TRT) is explored as a method to target hypoxic tumor cells.
Purpose of the Study:
- To review the potential of TRT in eradicating hypoxic cancer cells.
- To evaluate different TRT strategies using various particle types.
- To identify future research directions for optimizing TRT in hypoxic tumors.
Main Methods:
- Review of published literature on TRT strategies for hypoxic tumors.
- Analysis of TRT approaches utilizing beta-particles, alpha-particles, and Auger electrons.
- Discussion of dosimetry and radiobiology in the context of hypoxic tumor areas.
Main Results:
- Alpha-particle emitting radionuclides show significant promise due to their ability to induce DNA double-strand breaks irrespective of oxygen levels.
- TRT strategies using beta-particles, alpha-particles, and Auger electrons have been investigated.
- Dosimetry and radiobiology are crucial for understanding TRT efficacy in hypoxic environments.
Conclusions:
- Alpha-particle emitting radionuclides are the most promising TRT approach for hypoxic cancer cells.
- Further research with improved in vitro and in vivo models is needed.
- Combination TRT strategies may be essential for achieving long-term anti-tumor efficacy.
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