title: Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation.
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.
authors.affiliation: Brigham and Woman's Hospital, Harvard Medical School, Boston, MA, USA. Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Brivio
authors.forename: P
authors.initials: P
authors.lastname: Zygmanski
authors.forename: M
authors.initials: M
authors.lastname: Arnoldussen
authors.forename: J
authors.initials: J
authors.lastname: Hanlon
authors.forename: E
authors.initials: E
authors.lastname: Chell
authors.forename: E
authors.initials: E
authors.lastname: Sajo
authors.forename: G M
authors.initials: GM
authors.lastname: Makrigiorgos
authors.forename: W
authors.initials: W
authors.lastname: Ngwa
mesh_terms: D004730:Endothelium, Vascular / Q000473:pathology* / Q000528:radiation effects; D005123:Eye / Q000503:physiopathology / Q000528:radiation effects; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008268:Macular Degeneration / Q000473:pathology / Q000601:surgery*; D053768:Metal Nanoparticles / Q000737:chemistry*; D009010:Monte Carlo Method; D009389:Neovascularization, Pathologic; D016634:Radiosurgery / Q000379:methods*; D014965:X-Rays
chemical_list: D006046:Gold