Methods and techniques for preclinical in vivo evaluation of radiosensitivity and radioresponsivity

Over the years, radiotherapy (RT) has considerably broadened the possibility for treating tumors and led to an overall improvement in the quality of life of cancer patients. Cancer-cell radiosensitivity and radioresponsivity, being related to patient-specific tumor features and conditions, such as proliferation rate, metabolism, percentage of apoptosis, new vessel formation and level of hypoxia, influence the efficacy of RT treatment. Radiosensitivity and radioresponsivity can now be studied in the clinical setting using in vivo molecular imaging techniques, such as positron emission tomography, single photon emission tomography and magnetic resonance imaging. Furthermore, the availability of many new radiotracers and imaging probes is improving the approach to the exploration of tumor response to RT. However, to be successful in clinical, in vivo imaging investigations require an in-depth understanding of the molecular basis of tumor response to RT. Small-animal models of neoplasia are now an essential tool for the preclinical evaluation of novel anti-neoplastic therapies, also at molecular level. However, the accuracy of RT techniques for small animal needs to be improved. Indeed, human conformal RT devices are less accurate when used in small-animal irradiation, which involves relatively small radiation fields and demands more precise beam localisation than is typical of clinical irradiators. The aim of this paper is to review current preclinical protocols and small-animal models for the in vivo study of radiosensitivity and radioresponsivity. More-over, the new solutions for dedicated small-animal conformal RT devices are also analyzed.