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Emerging targeted radiation therapies: simulations and benchmarking of cellular response to radiation.

Department of Physics

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About the Project

Ionizing radiation is a highly effective way to treat cancer. It is used in about 50% of all cancer patients, either alone or in combination with surgery or chemotherapy. When using external beams of radiation, however, healthy tissue and organs at risk in the beam path and in close proximity to the tumor often experience significant radiation dose as well. The resulting damage can limit how much dose can be administered to the tumor and consequently the treatment outcome. A very important part of cancer research is to increase the damage to the cancer while decreasing the damage to the surrounding tissue - increasing the therapeutic index.
A relatively new treatment method, targeted radiation therapy (TRT), promises to do exactly that. This is gaining rapidly in popularity due to its potential to treat wide-spread metastasis of cancer which previously could not be treated with external beam therapy as too much of healthy tissue would have been affected. In targeted radiation therapy (TRT) e.g. with Lu-177, and especially its subgroup targeted alpha therapy (TAT), e.g. with Ac-225, radio-nuclei are attached to a targeting vector, e.g. a peptide. This vector, via biochemical or other mechanisms accumulates preferentially close to or even inside the cancer cells. There, the radio-nuclei decay and cause a highly localised damage to cancer cells and leads to effective tumor control, and through several mechanisms to cancer cell death, while greatly minimizing the damage to surrounding healthy tissue.
Many fundamental aspects of TRT are, however, yet not fully explored. For example, what is the optimal targeting vector? Which radio-nuclei are most suitable candidates for TRT? How close does the TRT drug need to be to the cancer cell or the cancer cell nucleus for an effective treatment? If the radio-nuclei have a decay chain, how does the recoil momentum from a previous decays affect the drug composition and position? What radiation dose needs to be delivered for effective tumor control? How can quantitative dosimetry to the cancer and other organs be assessed during the treatment?

The present project will address some of these fundamental questions. It will firstly focus on simulation of the cellular response (single-cell dose level) to TRT, depending on the targeting vectors affinity to the cell and stability during the treatment process. The project will include:
- Building a Geant4-based framework for simulation of the cellular response for a range of different TRT;
- Assessment of the impact on single-cells and multi-cell clusters, including the impact on nearby healthy cells and the response for a range of cell types;
- Quantitative evaluation of the efficiency of different categories of radio emitters (established and novel), including the impact of radioactive decay chains for the treatment.

In extension of the simulation work, the project will furthermore include planning (designing) of future experiments which could quantitatively assess the single-cell response to high dosage levels. This particularly includes design and proof-of-principle testing of nuclear radiation sensors for use in biochemical environments. New proposals for novel radio emitters for targeted radiation treatment will be explored based on the work, along with investigation of new production mechanisms for these radio-emitters.


Academic entry requirements: at least a class 2:1 MSc or MPhys degree in Physics.
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