Dosimetric Efficacy of Nanoparticle-Mediated Photon Radiotherapy

External beam radiotherapy has been instrumental in effectively treating and controlling cancer malignancies at various anatomical sites since the 1950s. During megavoltage photon therapy, the incident photons are scattered, causing secondary Compton electrons to subsequently deposit their energy within the tissue though ionisation processes. It is this energy transfer that results in the majority of the dose to the tumour volume.

In more recent decades, efforts have been focused on increasing the effectiveness of radiotherapy through engineering more advanced linear accelerators, adopting enhanced planning techniques and increased rigor of quality control processes. This includes the support of image guided techniques to guarantee accurate spatial localisation of the treatment site, as well as the use of intensity modulated delivery which generates treatments with a high degree of conformality to the tumour.

In the field of nanotechnology, functionalised gold nanoparticles (AuNPs) have had promising results within alternative modalities for both the diagnostic and treatment component of the patient's cancer pathway. An example of their utility includes Raman nanotheranostic (RaNT) technologies that aims to provide minimally invasive early detection and therapy for cancerous tissues [1][2].

Furthermore since 2004 [3], gold nanostructures have been the research focus of potentially improving the efficacy of current radiation therapies by raising the effective treatment dose within the vicinity of the tumour, hence inducing DNA strand damage. This is promising as a concern for clinical physicists is that treatment planning requires a compromise of maximising the tumour control, whilst having the required dosimetric conformality for reducing associated toxicities in the surrounding tissues.

As part of a literature review, Sohyoung et al. [4] expressed that whilst a number of publications within a pre-clinical setting corroborated the benefits of incorporating AuNPs in radiotherapy, its translation into clinical context needs to be better supported.

It is intended that this project will contribute to this area by investigating the dosimetric improvement from introducing nanoparticles of select properties within a patient representative in-vitro medium or cell culture. This would reflect a potential clinical stage where external beam therapy would be coupled with intravenous injection of nanoparticles.

Justifying the use of nanoparticles within the megavoltage energy range also poses a challenge, as the photoelectric effect that causes localised dose amplification is relatively supressed [2]. However, dosimetric enhancement is not negligible as reported from Monte Carlo simulations [5]. These energies are also important in common radical radiotherapy treatments for deep seated tumours.

To approach this issue, the media will be exposed to radiation beams of standard megavoltage treatment energies. Therefore, the project will focus efforts on investigating and providing insights into what recommendations should be made regarding the choice of radiosensitising agent to achieve a valuable dosimetric benefit within this energy regime.

This project supports the alignment with the EPSRC healthcare technologies theme by reflecting a clinical need to develop more effective cancer treatment strategies. The theme underpinning this proposal is multidisciplinary, addressing the healthcare challenge within oncology of maximising tumour control in radiotherapy using the physics of particle interactions.

Despite this field being at the early stage of development from a clinical implementation perspective, the results can have a strong hospital translation since therapeutic linear accelerators are in widespread utility in a number of NHS oncology centres across the UK and globally.