ESTRO 36 Abstract Book

S214 ESTRO 36 _______________________________________________________________________________________________

SP-0402 Strategies for radiosensitization with gold nanoparticles S. Krishnan 1 1 UT MD Anderson Cancer Center Radiation Physics, Houston- TX, USA Radiation therapy is a long-established component of modern therapy for localized cancers. However, its ultimate utility is limited by the inherent resistance of some cancer cells to ionizing radiation. To circumvent this problem, radiation dose escalation, targeting resistance pathways or resistant cells with novel agents, or image- guided tumor-targeted therapy are currently being investigated. Emerging evidence from an explosion of knowledge and research regarding oncologic uses of gold nanoparticles suggests that unique solutions to each of these problems of radiation resistance can be formulated via the use of gold nanoparticles. Gold nanoparticles can be used to augment the efficacy of radiation therapy via physical dose enhancement based on an increase in photoelectric absorption due to the high atomic number (Z) of gold that accumulates preferentially within the tumor due to passive extravasation of nanoparticles through “leaky” tumor vasculature. This radiation dose enhancement can be heightened via biological targeting. Enhancement of radiation therapy efficacy can also be achieved via extrinsic actuation of tumor-homing nanoparticles to generate mild temperature hyperthermia which enhances vascular perfusion and reduces hypoxia initially and causes vascular disruption subsequently to improve radioresponse. The extrinsic energy source is light for colloidal gold nanoparticles with a large absorption cross section that absorb and scatter light strongly at a characteristic wavelength (their plasmon resonance) and have a high thermal conductivity to couple this heat to the surrounding tissue. The interface between nanotechnology and radiation oncology warrants continued investigation by interdisciplinary teams of physicists, chemists, biologists, clinicians, and engineers in industry and academia. This talk will review the current understanding of the use of gold nanoparticles as radiosensitizers, and outline a path to potential clinical translation of these concepts of radiation sensitization. SP-0403 Potentials of Cerenkov imaging in radiotherapy A. Spinelli 1 1 Fondazione Centro San Raffaele, Medical Physics, Milano, Italy In this talk we will provide an overview of Cerenkov radiation (CR) production mechanism, we will then show examples of Cerenkov luminescence imaging (CLI) of small animals and humans. The potential uses of CLI for quality assurance (QA) and real time in vivo dosimetry during external-beam radiation therapy (RT) will be also presented. The mechanism of CR production is quite unique with respect to other and more common charged particles and matter interaction mechanisms. In this case when a charged particle travels through a dielectric medium, it becomes locally polarized, with the atoms comprising the medium behaving such as elementary dipoles. If the speed of the particle is less than the speed of light in the medium, symmetry of the polarization results in a negligible field at larger distances. However, if the particle's speed exceeds that light in this medium, the polarization field becomes asymmetric along the particle track producing a resultant dipole field at larger distances from the track [1]. For a beta particle travelling in water the energy threshold for Cerenkov emission is equal to 261 keV. This energy threshold is relatively low and thus CLI can be applied to image most of the beta plus and minus emitters commonly

cancer patients have been treated with the grid technique using high-energy linac-generated photon beams. Grid therapy has normally been considered only when other treatment options have failed. For that reason, only sporadic cases with advanced disease and large bulky tumours have been treated with grid therapy. Large in- beam peak doses, e.g. 15 Gy, have been given to the target volume in a single treatment fraction. Although certain sub-volumes of the target (in-between the beams) are given low doses, significant reductions of the size of large tumours have been demonstrated. Grid therapy has been found to produce limited toxicity in the surrounding sensitive tissues. The high normal-tissue tolerance to beam grids is closely related to the so-called dose-volume effect which has been characterized for single beams. Experiments with beam sizes in the millimetre to centimetre range with both proton- and photon-beams have demonstrated that the tolerance doses for various biological endpoints, e.g . different skin reactions and nervous-system white-matter necrosis, are rising with reduced beam sizes. Research carried out within the American space exploration program in the 1950s showed that the tolerance doses increased dramatically for micrometer-wide beams. Certain endpoints, e.g. moist desquamation, are never observed for sufficiently small beam widths, even for extremely high doses. The migration of cells from unirradiated to irradiated volumes and an improved vascular repair if only a short segment of a vessel is irradiated have been stated as reasons for the improved tissue repair observed. Experiments and preclinical radiotherapy trials with photon- and ion-beam grids, containing beam elements of widths in the micrometre to millimetre range, have recently been carried out. These experiments have demonstrated the high degree of normal-tissue tolerance to irradiation with grids of narrow beams up to doses (hundreds of Grays) which are much higher than those used clinically. In ongoing radiobiological research, there are still some open questions regarding the tumour response to spatially modulated beams. A differential effect on the tumour vasculature has been reported. The so-called bystander effect has also attracted many researchers´ interests. However, the direct effects of radiation, due to radiation that directly hits the cell nuclei and cause DNA double- strand breaks, are generally believed to be much more important for the cell survival. Whether the bystander effect significantly changes the outcome of grid therapy has not been proven because both beneficial and destructive bystander responses have been reported. The x-ray beams produced by the early machines were of low energy and highly divergent. Therefore, the beam elements in the grid began to overlap already close to the patient surface. The large divergence made it difficult to produce a tissue-sparing effect at larger depths and also made it nearly impossible to produce a uniform dose in the target by cross-firing irradiation grids with opposing beams. Nowadays, more parallel x-ray beams of high energy and fluence rate are available. Thus, there is a real possibility to exploit the normal-tissue sparing effect of radiation grids for the treatment of more deep-seated organs. Development in beam technology has provided new possibilities to cross-fire radiation grids with the aim of producing a uniform dose in the target volume. Furthermore, beams containing charged particles, e.g. electrons, protons and carbon ions, have recently been suggested for use in grid therapy. The limited range, and the sometimes increased radiobiological effectiveness of charged-particle beams, may be found advantageous. Some results from the most recent research on grid therapy will be shown in this presentation.