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.
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