The use of gold nanoparticles for tumour dose enhancement from microbeam radiotherapy

Gold nanoparticles (AuNPs) are currently being trialled for use in a range of medical applications, including as a contrast agent for imaging tumours and radiotherapy. AuNPs have been shown to have a preferential uptake into tumorous cells over normal cells in vivo. As a result AuNPs could act as dose enhancers in radiotherapy, by providing a relative abundance of electrons for x-rays to ionise, in comparison to regular tissue. The use of AuNPs for dose enhancement with microbeam radiotherapy (MRT) techniques has been examined in this study. The chief findings of this research are: <br>[1] Monte Carlo simulations predict that the addition of AuNPs uniformly through tissue is not sufficient to produce a useful dose enhancement to a tumour volume at a clinically relevant depth. However, when the target concentration is 7 mg Au/g compared to the surrounding tissue’s 2 mg Au/g, then the dose enhancement factor rises to 1.87 for a broadbeam spectrum from BL28B2 at SPring-8 synchrotron. <br>[2] The important peak-to-valley dose ratio (PVDR) of a microbeam is reduced by the presence of sufficient gold in tissue. The PVDR reduces from 158:1 ±9 to 80:1 ±3 for 7 mg Au/g tissue, and 54:1 ±2 for 18 mg Au/g tissue. <br>[3] PRESAGE dosimeters have been discovered to be readable via fluorescent microscopy from a 638 nm laser. This florescence has been used to measure the PVDR of BL28B2 at SPring-8 synchrotron to be 52:1, compared to 30:1 using EBT2 film dosimetry under similar conditions. <br>[4] The ability of in vitro cells to fill a scratch or wound is impaired by the presence of AuNPs, with the gap-filling time increasing with higher AuNP concentrations, for both rat glioma (RG2) and bovine aortic endothelial (BAEC) cells. <br>[5] For MRT, the dose enhancement factors (DEFs) for tumorous and non-tumorous cells in vitro for 1 mM AuNPs have been calculated and found to be approximately equivalent, with the DEFs for RG2 and BAEC cells being 1.68±0.12 and 1.62±0.13, respectively. With a preferential accumulation of AuNPs in a tumour in vivo, this means that tumorous tissue can receive a larger dose, and thereby recover less from AuNP-enhanced MRT.<br>