Beam Energy Considerations for Gold Nano-Particle Enhanced Radiation Treatment

📝 Abstract

Purpose: A novel approach using nano technology enhanced radiation modalities is investigated. The proposed methodology uses antibodies labeled with organically inert metals with a high atomic number. Irradiation using photons with energies in the kilo–electron volt (keV) range show an increase in dose due to a combination of an increase in photo-electric interactions and a pronounced generation of Auger and/or Coster-Kronig (A-CK) electrons. Methods: The dependency of the dose deposition on various factors is investigated using Monte Carlo simulation models. The factors investigated include: agent concentration, spectral dependency looking at mono–energetic sources as well as classical bremsstrahlung sources. The optimization of the energy spectrum is performed in terms of physical dose enhancement as well as the dose deposited by Auger and/or Coster-Kronig electrons and their biological effectiveness. Results: A quasi-linear dependency on concentration and an exponential decrease within the target medium is observed. The maximal dose enhancement is dependent on the position of the target in the beam. Apart from irradiation with low photon energies (10 - 20 keV) there is no added benefit from the increase in generation of Auger electrons. Interestingly, a regular 110kVp bremsstrahlung spectrum shows a comparable enhancement in comparison with the optimized mono–energetic sources. Conclusions: In conclusion we find that the use of nano-particle enhanced shows promise to be implemented quite easily in regular clinic on a physical level due to the advantageous properties in classical beams.

💡 Analysis

Purpose: A novel approach using nano technology enhanced radiation modalities is investigated. The proposed methodology uses antibodies labeled with organically inert metals with a high atomic number. Irradiation using photons with energies in the kilo–electron volt (keV) range show an increase in dose due to a combination of an increase in photo-electric interactions and a pronounced generation of Auger and/or Coster-Kronig (A-CK) electrons. Methods: The dependency of the dose deposition on various factors is investigated using Monte Carlo simulation models. The factors investigated include: agent concentration, spectral dependency looking at mono–energetic sources as well as classical bremsstrahlung sources. The optimization of the energy spectrum is performed in terms of physical dose enhancement as well as the dose deposited by Auger and/or Coster-Kronig electrons and their biological effectiveness. Results: A quasi-linear dependency on concentration and an exponential decrease within the target medium is observed. The maximal dose enhancement is dependent on the position of the target in the beam. Apart from irradiation with low photon energies (10 - 20 keV) there is no added benefit from the increase in generation of Auger electrons. Interestingly, a regular 110kVp bremsstrahlung spectrum shows a comparable enhancement in comparison with the optimized mono–energetic sources. Conclusions: In conclusion we find that the use of nano-particle enhanced shows promise to be implemented quite easily in regular clinic on a physical level due to the advantageous properties in classical beams.

📄 Content

arXiv:0912.3899v1 [physics.med-ph] 19 Dec 2009 Beam Energy Considerations for Gold Nano–Particle Enhanced Radiation Treatment F. Van den Heuvel Ph.D.∗1, Jean–Pierre Locquet Ph.D.2 and S. Nuyts M.D. Ph.D.1 Dept of Experimental Radiotherapy University of Leuven, Leuven, Belgium E-mail: (∗)frank.vandenheuvel@med.kuleuven.be Solid State Physics and Magnetism Section University of Leuven, Leuven, Belgium Abstract. Purpose: A novel approach using nano technology enhanced radiation modalities is investigated. The proposed methodology uses antibodies labeled with organically inert metals with a high atomic number. Irradiation using photons with energies in the kilo–electron volt (keV) range show an increase in dose due to a combination of an increase in photo–electric interactions and a pronounced generation of Auger and/or Coster–Kr¨onig (A–CK) electrons. Methods: The dependency of the dose deposition on various factors is investigated using Monte Carlo simulation models. The factors investigated include: agent concentration, spectral dependency looking at mono–energetic sources as well as classical bremsstrahlung sources. The optimization of the energy spectrum is performed in terms of physical dose enhancement as well as the dose deposited by Auger and/or Coster–Kr¨onig electrons and their biological effectiveness. Results: A quasi–linear dependency on concentration and an exponential decrease within the target medium is observed. The maximal dose enhancement is dependent on the position of the target in the beam. Apart from irradiation with low photon energies (10 – 20 keV) there is no added benefit from the increase in generation of Auger electrons. Interestingly, a regular 110kVp bremsstrahlung spectrum shows a comparable enhancement in comparison with the optimized mono–energetic sources. Conclusions: In conclusion we find that the use of nano–particle enhanced shows promise to be implemented quite easily in regular clinic on a physical level due to the advantageous properties in classical beams. Nano–particle enhanced radiation treatment 2

1. Introduction Recently, methodologies using monoclonal antibodies that target specific tumor cells have been used to bring active compounds in the vicinity of these cells. One approach uses radioactive compounds of α– or β–emitters[1, 2, 3]. Alternatively, chemotherapeutic compounds have been attached to this delivery mechanism. The use of such approaches is interesting but limited due to the fact that the therapeutic compound is already active at time of delivery and during secretion by the body. More in particular with radioactive compounds an important whole body dose (red marrow dose) as well as renal toxicity are limiting factors for the efficacy of the treatment[4, 5, 6, 7]. It is the goal of this paper to investigate a delivery method that could potentially have most of the benefits associated with the previously listed therapeutic modalities ´and has almost none of the disadvantages. Which means: (i) Differentiation between malignant and healthy cells. (ii) Enhanced effectiveness. (iii) Image guidance possibilities. (iv) Activation methodology (i.e. Only active were it needs to be active). (v) Large therapeutic window. Dose enhancement due to the presence of gold nano–particles has been proposed already both by means of an injectable contrast agent as by the use of mono–clonal antibodies or other targetted delivery methods.. However, the enhancement relied on an increased interaction due to the increased probability of the photo–electric interaction being dependent on the atomic number at the proposed energies and the specific contribution of Auger electrons was not investigated[8, 9, 10, 11]. All sources used in these studies were spectral sources and/or brachytherapy sources. Moreover, proposals to use more sophisticated photon sources have been put forward, in the hope to maximize the efficiency of the conversion of the beam energy to deposited energy as well as generate a high amount of Auger electrons[12]. In the dose deposition model proposed here a significant part of the energy is deposited by Auger electrons. There is reason to believe that Auger electrons deposit their energy more efficiently than those emanating from Compton or photo–electric effect processes. The exact mechanism behind this apparant dose enhancement effect is still unclear. A possible cause is the fact that Auger have a very low energy and deposit all of the energy within a range comparable to a few cell diameters. Furthermore, there is a possible change in the stopping power energy dependency at very low energies (<10keV), where the Bethe formalism breaks down. Alternatively, it could be that on average more than a single Auger electron is being produced, increasing the probability of clustered double strand breaks. A number of authors have investigated the biological effects indirectly and support the notion that Auger electrons indeed have high LET characteristics[13, 14, 15]. To our knowledge. a

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