Radiotherapy by Photoactivation of Iron Nanoparticles and Mössbauer effect
Résumé
The Mössbauer effect [1], the resonant and recoil-free absorption and subsequent re-emission of γ rays by Mössbauer isotopes (e.g. 57Fe) leads to the emission of many Auger electrons (a single Auger event is comparable to more than 105 photon absorption events). These high LET electrons can induce clustered DNA damages (including Double Strand Breaks (DSB) and Locally Multiple Damaged Sites (LMDS)) if emitted in the direct vicinity of DNA. Dose (in J/kg) enhancement using Mössbauer effect has been first described in vitro by Mills et al. [2]. Since then, several studies have obtained conflicting results. The divergence of the data is mainly due to stringent experimental conditions mandatory to get Mössbauer resonance: photon energy of 14.4 keV (for 57Fe), crystalline network of the atom… Since Synchrotron radiation properties are well suited for Mössbauer resonance (high fluence and precise control on the irradiation energy), we propose to evaluate the efficiency of iron nanoparticles (NPFe) enriched in 57Fe to enhance dose deposition during radiotherapy. A sharp increase is expected in presence of nanoparticles. A preliminary experiment has been carried out at the European Synchrotron Radiation Facility ID18 (Mössbauer-dedicated beamline). Under irradiation at 14.4 keV (delta E = 0.65 meV), NPFe (synthesized as Choi described previously [3]) embedded in agarose gel produce a Nuclear Inelastic Scattering spectrum giving a density of phonon states similar to bulk iron as measured by Handke [4]. This result indicates that Mössbauer interactions can happen at room temperature in NPFe in a material with tissue-like rigidity.
In parallel to this study, dose-enhancement produced by the photoelectric effect was also evaluated. F98 rodent glioma cells incubated with NPFe and irradiated at various monochromatic energies on the Beamline ID17 (30 to 80 keV) present a decreased survival rate due to photoelectrons produced by the interactions of low energy radiations with heavy atoms. We observed by ICPMS a very high concentration of the same alginate-coated magnetite nanoparticles in F98 rat glioma cells after 24h of incubation, up to a hundred of pg/cell. Those results have been confirmed by a 2D-X Ray microfluorescence experiment at the ID16B Beamline of the ESRF, showing high concentration of nanoparticles around the nucleus.
To conclude, the performed experiments refine our comprehension of the physics of Mössbauer interactions, as well as confirm the theoretical basis for its application to enhance radiotherapy efficacy, and provide nanoparticles suitable to continue the study.
References
[1] - R. L. Mössbauer, Z. Physik 151, pp. 124-143 (1958).
[2] - Mills et al., Nature 336, pp. 787-789 (1988).
[3] - Choi et al., Radiation Oncology 7, 184 (2012).
[4] – Handke et al., PRL B 71, 144301 (2005).