Recently, interactions of x-rays with gold nanoparticles (GNPs) and the resulting dose enhancement have been studied using several Monte Carlo (MC) codes (Jones et al 2010 Med. Phys. 37 3809–16, Lechtman et al 2011 Phys. Med. Biol. 56 4631–47, McMahon et al 2011 Sci. Rep. 1 1–9, Leung et al 2011 Med. Phys. 38 624–31). These MC simulations were carried out in simplified geometries and provided encouraging preliminary data in support of GNP radiotherapy. As these studies showed, radiation transport computations of clinical beams to obtain dose enhancement from nanoparticles has several challenges, mostly arising from the requirement of high spatial resolution and from the approximations used at the interface between the macroscopic clinical beam transport and the nanoscopic electron transport originating in the nanoparticle or its vicinity. We investigate the impact of MC simulation geometry on the energy deposition due to the presence of GNPs, including the effects of particle clustering and morphology. Dose enhancement due to a single and multiple GNPs using various simulation geometries is computed using GEANT4 MC radiation transport code. Various approximations in the geometry and in the phase space transition from macro- to micro-beams incident on GNPs are analyzed. Simulations using GEANT4 are compared to a deterministic code CEPXS/ONEDANT for microscopic (nm–µm) geometry. Dependence on the following microscopic (µ) geometry parameters is investigated: µ-source-to-GNP distance (µSAD), µ-beam size (µS), and GNP size (µC). Because a micro-beam represents clinical beam properties at the microscopic scale, the effect of using different types of micro-beams is also investigated. In particular, a micro-beam with the phase space of a clinical beam versus a plane-parallel beam with an equivalent photon spectrum is characterized. Furthermore, the spatial anisotropy of energy deposition around a nanoparticle is analyzed. Finally, dependence of dose enhancement on the number of GNPs in a finite cluster of nanoparticles is determined. Simulations were performed for 100 nm GNPs irradiated in water phantom by various monoenergetic (11 keV–1 MeV) and spectral (50 kVp) sources. The dose enhancement ratio (DER) is very sensitive to the specific simulation geometry (µSAD, µS, µC parameters) and µ-source type. For a single GNP the spatial distribution of DER is found to be nearly isotropic with limited magnitude and relatively short range (∼100–200 nm for DER significantly greater than 1). For a cluster of GNPs both the magnitude and range are found much greater (∼1–2 µm). The relation between DER for a cluster of GNPs and a single GNP is strongly nonlinear. Relatively strong dependence of DER on the simulation micro-geometry cautions future studies and the interpretation of existing MC results obtained in different simulations geometries. The nonlinear relation between DER for a single and multiple GNPs suggests that parameters such as the number of adjacent nanoparticles per cell and the distances between the GNPs and the cellular target may be important in assessing the biological effectiveness associated with GNP.

We review radiation transport and clinical beam modelling for gold nanoparticle dose-enhanced radiotherapy using X-rays. We focus on the nanoscale radiation transport and its relation to macroscopi...

Nanoparticle-aided radiation therapy is emerging as a promising modality to enhance radiotherapy via the radiosensitizing action of high atomic number (Z) nanoparticles. However, the delivery of sufficiently potent concentrations of such nanoparticles to the tumor remain a challenge. This study investigates the dose enhancement to lung tumors due to high-Z nanoparticles (NPs) administered via inhalation during external beam radiotherapy. Here NPs investigated include: cisplatin nanoparticles (CNPs), carboplatin nanoparticles (CBNPs), and gold nanoparticles (GNPs). Using Monte Carlo–generated megavoltage energy spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumors due to radiation-induced photoelectrons from the NPs administered via inhalation route (IR) in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung via IV. Meanwhile recent experimental studies indicate that 3.5–14.6 times higher concentrations of NPs can reach the lung by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the radiotherapy dose with and without nanoparticles was calculated for a range of NPs concentrations and tumor sizes. The DEF for IR was then compared with that for IV. For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of up to 1.19, 1.26, and 1.51 were obtained for CNPs, CBNPs and GNPs. In comparison values of 1.06, 1.08, and 1.15 were obtained via IV administration. For IR with 14.6 times higher concentrations, even higher DEF values were obtained e.g. 1.81 for CNPs. Results also showed that the DEF increased with increasing field size or decreasing tumor volume, as expected. The results of this work indicate that IR administration of targeted high-Z CNPs/CBNPs/GNPs could enable clinically significant DEF to lung tumors compared to IV administration during external beam radiotherapy. For FDA approved concentrations of CNPs or CBNPs considered, this could allow for additional dose enhancement to tumors via photoelectric mechanism during concomitant chemoradiotherapy.

Studies show that radiotherapy of a primary tumor in combination with immunoadjuvants (IA) can result in increased survival or immune-mediated regression of metastasis outside the radiation field, a phenomenon known as abscopal effect. However, toxicities due to repeated systematic administration of IA have been shown to be a major obstacle in clinical trials. To minimize the toxicities and prime a more potent immune response, Ngwa et al have proposed that inert radiotherapy biomaterials such as fiducials could be upgraded to multifunctional ones loaded with IA for in situ delivery directly into the tumor sub-volume at no additional inconvenience to patients. In this preliminary study, the potential of such an approach is investigated for lung cancer using anti-CD40 antibody. First the benefit of using the anti-CD40 delivered in situ to enhance radiotherapy was tested in mice with subcutaneous tumors generated with the Lewis Lung cancer cell line LL/2 (LLC-1). The tumors were implanted on both flanks of the mice to simulate metastasis. Tumors on one flank were treated with and without anti-CD40 and the survival benefits compared. An experimentally determined in vivo diffusion coefficient for nanoparticles was then employed to estimate the time for achieving intratumoral distribution of the needed minimal concentrations of anti-CD40 nanoparticles if released from a multifuntional radiotherapy biomaterials. The studies show that the use of anti-CD40 significantly enhanced radiotherapy effect, slowing the growth of the treated and untreated tumors, and increasing survival. Meanwhile our calculations indicate that for a 2–4 cm tumor and 7 mg g⁻¹ IA concentrations, it would take 4.4–17.4 d, respectively, following burst release, for the required concentration of IA nanoparticles to accumulate throughout the tumor during image-guided radiotherapy. The distribution of IA could be customized as a function of loading concentrations or nanoparticle size to fit current Stereotactic Body Radiotherapy schedules. Overall, the preliminary results support ongoing work in developing multifunctional radiotherapy biomaterials for in situ delivery of immunoadjuvants such as anti-CD40 to leverage the abscopal effect, while minimizing systemic toxicities. The potential of extending such an approach to other cancer types is discussed.