ABSTRACT
This work uses Monte Carlo radiation transport simulation to assess the potential benefits of gold nanoparticles (AuNP) in the treatment of neovascular age-related macular degeneration with stereotactic radiosurgery. Clinically, a 100 kVp x-ray beam of 4 mm diameter is aimed at the macula to deliver an ablative dose in a single fraction. In the transport model, AuNP accumulated at the bottom of the macula are targeted with a source representative of the clinical beam in order to provide enhanced dose to the diseased macular endothelial cells. It is observed that, because of the AuNP, the dose to the endothelial cells can be significantly enhanced, allowing for greater sparing of optic nerve, retina and other neighboring healthy tissue. For 20 nm diameter AuNP concentration of 32 mg g(-1), which has been shown to be achievable in vivo, a dose enhancement ratio (DER) of 1.97 was found to be possible, which could potentially be increased through appropriate optimization of beam quality and/or AuNP targeting. A significant enhancement in dose is seen in the vicinity of the AuNP layer within 30 µm, peaked at the AuNP-tissue interface. Different angular tilting of the 4 mm beam results in a similar enhancement. The DER inside and in the penumbra of the 4 mm irradiation-field are almost the same while the actual delivered dose is more than one order of magnitude lower outside the field leading to normal tissue sparing. The prescribed dose to macular endothelial cells can be delivered using almost half of the radiation allowing reduction of dose to the neighboring organs such as retina/optic nerve by 49% when compared to a treatment without AuNP.
Subject(s)
Endothelium, Vascular/pathology , Gold/chemistry , Macular Degeneration/surgery , Metal Nanoparticles/chemistry , Monte Carlo Method , Neovascularization, Pathologic , Radiosurgery/methods , Endothelium, Vascular/radiation effects , Eye/physiopathology , Eye/radiation effects , Humans , Macular Degeneration/pathology , X-RaysABSTRACT
PURPOSE: This work determines how variations in eye size will influence the radiation absorbed dose delivered to non-targeted tissues within the eye during stereotactic radiosurgery of age-related macular degeneration (AMD) using the IRay™ treatment. METHODS: Stylized models of the eye were created with axial lengths of 20, 22, 24, 26, and 28mm. Each model was based upon the reference eye model from NCRP Report 130 and then scaled appropriately for each axial length. Models were incorporated with MCNPX radiation transport code in order to simulate the three beam IRay™ delivery system. Simulation results were assessed for both the mean absorbed dose and dose-volume histograms (DVH) for both target (macula) and non- targeted eye tissues, including the lens, retina, central retinal artery, and optic nerve. RESULTS: For each of the three beams, an average dose of 8Gy was delivered to the macula resulting in a total average dose of 24Gy for each eye model. The lens of the eye received a total average dose ranging from 146 to 189mGy, with the larger doses occurring in the smaller eye models since the beams traverse through the sciera closer to the limbus. The distal tip (1.5mm) of the central retinal artery received a total average dose ranging from 499 to 567mGy, with the larger doses occurring in the larger eye models due to increased scatter resulting from longer tissue path length to the nominal target. The optic nerve received a total average dose ranging from 207 to 225mGy, with the larger doses occurring in the smaller eye models. CONCLUSIONS: The small variation in dose to the lens, central retinal artery, and optic nerve suggests that eye size does not significantly affect radiation dose to non-targeted eye tissues. This work was sponsored by Oraya Therapeutics.
