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While these methods are effective, the dose delivered to healthy tissue remains one of the primary limiting factors in current radiation therapy. One approach to mitigate this issue is to attempt to increase the amount of dose deposited in the tumour compared to healthy tissue, which can potentially be achieved through the use of contrast agents.
X-ray contrast agents are those materials which absorb radiation much more strongly than the tissues of the body - below is plotted a comparison of the absorption of gold and soft tissue, at a range of energies.
It can be seen that, in the kilovoltage region (from 10 to 100 keV), gold absorbs roughly 100 times more energy than an equivalent mass of tissue. This means that, if it gold could be preferentially delivered to a tumour site, the dose in the tumour could be significantly increased without any adverse effects in healthy tissues for a therapy using such energies.
The primary challenge associated with this approach is the delivery of the gold to the tumour volume, which can be addressed through the use of gold nanoparticles. Specifically, it has been shown that gold nanoparticles preferentially accumulate in tumour sites in mice, allowing for relatively straightforward delivery of gold to tumours.
We have extrapolated these results using Monte Carlo radiation transport models to show that, if similar levels of uptake can be achieved in humans, there exists a significant potential to improve the dose distribution delivered to target tumours.
The above image illustrates an example of this - a CT slice of a neck volume (top left) is voxelised and imported into the GEANT4 radiation transport code, with the addition of a "tumour" volume, containing a gold nanoparticle contrast agent (top right).
The exposure of this geometry to either LINAC (bottom left) or tuned kilovoltage radiation (bottom right) was then modelled. The bottom right plot shows a clear improvement in dose specificity to the tumour volume, indicating the potential for improved therapeutic outcomes.
This result was expanded to include the consideration of a wider range of tumour positions, with the above plot showing which of three sources (two kilovoltage, and one LINAC) offers superior dose distributions with different combinations of tumour depth and target thickness.
It can be seen that for a large range of possible geometries, and a correspondingly large number of tumour classes, the combination of gold nanoparticles and kilovoltage X-rays offers a significant treatment benefit.
However, the above calculations are only based on the physical dose enhancement - that is, the additional energy which would be deposited in the tumour. What is less well understood is the effects that the introduction of gold nanoparticles would have on the chemistry and biology of the system, which is something that is being actively investigated in our group.
This work includes
- Investigating the effects of gold nanoparticles on the radio-sensitivity of cells,
- Making use of the plasmid system to allow the investigation of the effects of chemical environment on nanoparticle dose enhancement, and
- Exploring the energy dependence of nanoparticle dose enhancement using the Diamond synchrotron.