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 (AMD) 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, 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 um, 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.

Anti‐Flt1 peptide and cyanine‐conjugated gold nanoparticles for the concurrent antiangiogenic and endothelial cell proton treatment

“…Site‐specific CNR, which is induced by high‐Z Au in Flt1@AuNP‐HCy5.5 following VEGFR‐transcytosis delivery to HRMECs, resulted in a 60–80% increase in cytotoxicity. The nanoradiator effect of Flt1@AuNP‐HCy5.5 can be potentially derived from either X‐ray or ion beams. Considering the depth‐dose distribution, traversing proton‐irradiated CNR therapy may be applied to the target more safely without energy dissipation on the adjacent normal tissue than broadband X‐ray radiotherapy with bare AuNPs to remove newly formed or chronic NV in diseased retina.…”

“…The nanoradiator effect of Flt1@AuNP‐HCy5.5 can be potentially derived from either X‐ray or ion beams. Considering the depth‐dose distribution, traversing proton‐irradiated CNR therapy may be applied to the target more safely without energy dissipation on the adjacent normal tissue than broadband X‐ray radiotherapy with bare AuNPs to remove newly formed or chronic NV in diseased retina. Traversing proton beams induce the CNR effect without the deposition of Bragg peak energy inside the body, thus effectively generating site‐specific therapeutic beacons at the NP site .…”

“…Anti‐Flt1 AuNPs targeting to VEGFR‐1 may exhibit enhanced antiangiogenic properties that are useful for the treatment of neovascular diseases compared with bare AuNP. In addition to the antiangiogenic effects of AuNPs, they act as low‐energy electron‐releasing beacons when induced by either X‐ray photons or high‐energy proton beams, enabling site‐specific nanoradiator therapy. Targeted delivery of anti‐VEGF agents or antioxidant fluorescent agents to sites of oxidative stress associated with abnormal NV may significantly reduce retinal degeneration.…”

Emerging applications of nanotechnology for diagnosis and therapy of disease: a review

“…Researchers such as Brivio et al,(2015) [22] investigated the concept of kilovoltage radiosurgery with AuNPs for AMD (Age-related Macular Degeneration). They concluded that a prescribed dose of x-ray radiation could be delivered using almost half of the radiation when compared to a treatment without AuNPs allowing reduction of the dose delivered to the neighbouring organs such as the retinal/optic nerve by 49%.…”

A Monte Carlo study of I-125 prostate brachytherapy with gold nanoparticles: dose enhancement with simultaneous rectal dose sparing via radiation shielding

“…The shielding effect of high-Z barriers is well recognized and utilized for radiation protection. Similarly, nanoparticle-induced dose enhancement or radiosensitization has been demonstrated and investigated (Brivio et al 2015). However, although the attenuation of flux by tissues with AuNP has already been recognized (Toossi et al 2012, Van den Heuvel et al 2010), the simultaneous enhancement and trapping of radiation inside the tumor by using high-Z NP is a new concept and application of NP.…”