Abstract
Objective of the study: To explore the potential for therapeutic gain with gold nanoparticles in arteriovenous malformation radiosurgery based on their interaction with photons and protons. Study methods: Radiation dose enhancement resulting from the interaction of gold nanoparticles with irradiation ranging from kilovoltage to megavoltage photons and protons was researched in the literature. The role of angiogenesis and its regulation via vascular endothelial growth factors and cell membrane receptors, especially for endothelial cells in arteriovenous malformations, was investigated as a way for selective arteriovenous malformation deposition. Results: Radiation dose enhancement with gold nanoparticles is described in the literature but has so far only been investigated for its potential in treating malignancies. Because of the high atomic number of gold (Z = 79), dose enhancement occurs with photons mainly based on secondary photon and Auger electron production and the dose enhancement factor is the highest for irradiation with kilo voltage photons. Dose enhancement happens with megavoltage photons also but to a lesser extend and is mainly due to the ionization of gold by secondary photons and electrons generated by the megavoltage photons passing through tissue. The range of the secondary photo electrons emitted by gold is sufficient to cover the entire endothelial cell content. Protons interact with the production of Auger electrons which have a very short range, insufficient to cover the entire contents of endothelial cells, but sufficient to cause a high cell membrane dose for membrane located gold nanoparticles (AuNPs). Arteriovenous malformations are dynamic entities with angiogenesis taking place. This is reflected by a different expression of angiogenic receptors on the membrane of arteriovenous malformation endothelial cells compared to normal brain blood vessels, thereby opening the opportunity for selective deposition of such particles. For the use in proton therapy a new definition for the dose enhancement factor describing the local effect of nanoparticles is proposed. Conclusion: The concept of nanoparticle enhanced radiosurgery for arteriovenous malfor-mations by selective deposition of gold nanoparticles is a novel approach. The local dose enhancement opens the way for therapeutic gain which in turn could lead to improved obliteration rates and/or a shorter latent period.
Highlights
Radiosurgery is a well established therapeutic option for cerebral Arterio Venous Malformations (AVM), but the successful outcome is influenced by the AVM volume, its location, and the radiation dose that can safely be administered
The role of angiogenesis and its regulation via vascular endothelial growth factors acting on cell membrane receptors was investigated as a method to selectively concentrate gold nanoparticles in the AVM
The strongest enhancement is with kV energies with theoretical calculated Dose Enhancement Factor (DEF)’s in the range of 1.6 to 7.2 [30]
Summary
Radiosurgery is a well established therapeutic option for cerebral Arterio Venous Malformations (AVM), but the successful outcome is influenced by the AVM volume, its location, and the radiation dose that can safely be administered. There is always a latent time post radiosurgery until complete obliteration occurs. This latent time occurs with photons as well as with proton irradiation. Therapeutic response is dose related with higher doses increasing the obliteration rate. Complete obliteration is considered as a cure, but this is difficult to achieve for large AVMs with present radiosurgical techniques. To improve the results for large AVMs, the use of gold nanoparticles as radiation dose enhancers is explored
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