Chung K, et al. Radiat Oncol J. 2015 Dec;33(4):337-343. http://dx.doi.org/10.3857/roj.2015.33.4.337

Proton beams have been used for cancer treatment for more than 28 years, and several technological advancements have been made to achieve improved clinical outcomes by delivering more accurate and conformal doses to the target cancer cells while minimizing the dose to normal tissues. The state-of-the-art intensity modulated proton therapy is now prevailing as a major treatment technique in proton facilities worldwide, but still faces many challenges in being applied to the lung. Thus, in this article, the current status of proton therapy technique is reviewed and issues regarding the relevant uncertainty in proton therapy in the lung are summarized.

We investigated the feasibility of using multifunctional Fe ₃ O ₄ /TaO _x (core/shell) nanoparticles, developed for use in contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI), as dose-enhancing radiosensitizers. First, to verify the detectability of Fe ₃ O ₄ /TaO _x nanoparticles in imaging, in vivo tests were conducted. Approximately 600 mg kg ⁻¹ of 19 nm-diameter Fe ₃ O ₄ /TaO _x nanoparticles dispersed in phosphate-buffered saline was injected into the tail vein of six Balb/c mice used as tumour (4T1 mammary carcinoma cell) models. Three mice underwent MRI (BioSpec 70/20 USR, Bruker, Billerica, MA, USA) and micro-CT (Inveon, Siemens Preclinical, Knoxville, TN, USA) before and after the injection. The difference between the pre- and post-injection images was quantified by finding the correlation coefficient. The aorta, blood vessel, and liver were clearly seen in the MRI and micro-CT images 60 min after intravenous injection of Fe ₃ O ₄ /TaO _x nanoparticles, but the tumour region was not visible in the CT images until after 24 h. There were large differences between the pre- and post-injection images. Second, the therapeutic enhancement dose of nanomaterials was computed via Monte Carlo simulation. Monoenergetic 70- and 150 MeV proton beams irradiated x-ray contrast agent (iodine, BaSO ₄ ), MRI contrast agent (gadolinium, Fe ₃ O ₄ ), Au, Fe ₃ O ₄ /TaO _x (core/shell) nanoparticles and water located at the centre of a 4 × 4 × 4 µ m ³ water phantom, upon which the dose enhancement ratio (DER) (dose with/without nanoparticles) was computed. When 70 MeV protons irradiated the Au, gadolinium, Fe ₃ O ₄ /TaO _x , Fe ₃ O ₄ , iodine, and BaSO ₄ nanoparticles, the DERs at 1 nm were 15.76, 7.68, 7.82, 6.17, 4.85, and 5.51, respectively. Fe ₃ O ₄ /TaO _x nanoparticles have the potential to be used as a multifunctional agent that enhances tumour detection and increases the dose. Dose enhancement with Fe ₃ O ₄ /TaO _x was half that with Au. However, Fe ₃ O ₄ /TaO _x is much cheaper than Au, and it is expected that tumour targeting combined with magnetic field could overcome the low DER.

Gold nanoparticles (GNPs) injected in a body for dose enhancement in radiation therapy are known to form clusters. We investigated the dependence of dose enhancement on the GNP morphology using Monte-Carlo simulations and compared the model predictions with experimental data. The cluster morphology was approximated as a body-centred cubic (BCC) structure by placing GNPs at the 8 corners and the centre of a cube with an edge length of 0.22–1.03 µ m in a 4 × 4 × 4 µ m ³ water-filled phantom. We computed the dose enhancement ratio (DER) for 50 and 260 kVp photons as a function of the distance from the cube centre for 12 different cube sizes. A 10 nm-wide concentric shell shaped detector was placed up to 100 nm away from a GNP at the cube centre. For model validation, simulations based on BCC and nanoparticle random distribution (NRD) models were performed using parameters that corresponded to the experimental conditions, which measured increases in the relative biological effect due to GNPs. We employed the linear quadratic model to compute cell surviving fraction (SF) and sensitizer enhancement ratio (SER). The DER is inversely proportional to the distance to the GNPs. The largest DERs were 1.97 and 1.80 for 50 kVp and 260 kVp photons, respectively. The SF predicted by the BCC model agreed with the experimental value within 10%, up to a 5 Gy dose, while the NRD model showed a deviation larger than 10%. The SERs were 1.21 ± 0.13, 1.16 ± 0.11, and 1.08 ± 0.11 according to the experiment, BCC, and NRD models, respectively. We most accurately predicted the GNP radiosensitization effect using the BCC approximation and suggest that the BCC model is effective for use in nanoparticle dosimetry.