FTY720, sphingosine 1-phosphate receptor modulator, selectively radioprotects hippocampal neural stem cells.

Cranial irradiation is an effective treatment modality for both primary and metastatic brain tumors, yet it induces cognitive decline in a substantial number of patients. At present, there are no established methods for neuroprotection. Recent investigations have revealed a link between radiation-induced cognitive dysfunction and the loss of neural precursor cells in the hippocampus. Hence, identifying pharmacological agents, capable of protecting this cell population, is of interest. FTY720 (fingolimod), an FDA-approved oral drug for the treatment of multiple sclerosis, has been shown to promote the survival and differentiation of neural progenitors, as well as remyelination and repair after brain injury. In this study, we show that FTY720, used at nanomolar concentrations, is capable of increasing the viability and neurogenicity of irradiated neural stem cells from the hippocampus. In contrast, it does not provide radioprotection in a human breast cancer cell line and two glioma cell lines. These results suggest a potential therapeutic role for FTY720 as a neuroprotector during cranial irradiation. Further preclinical studies are warranted to evaluate this possibility.

HDR brachytherapy with surface applicators: technical considerations and dosimetry.

HDR surface molds offer an alternative radiotherapy modality to electrons for the treatment of skin lesions. Treatment planning and dosimetry are discussed for two types of surface molds used in our clinic. Standard rectangular applicators are used on a variety of sites where surface curvature is minimal. In these cases an idealized planar geometry is used for treatment planning dose calculations. The calculations yield treatment dose uniformity at the prescription depth in tissue as well as skin dose, as a percentage of the treatment dose, and its dose uniformity. The availability of optimization techniques results in superior dose uniformity at depth but the dose at the skin has to be carefully evaluated. We have studied the dependence of these dosimetric parameters on the size of the surface mold and the type of optimization procedure used in the dosimetry calculations. The second type of surface applicator involves the use of a customized silicone rubber mold attached to a thermoplastic mask of the patient. We have used them to treat lesions of the face where surface curvatures are appreciable and reproducibility of setup is more critical. In these cases a CT data set is used for reconstruction of the catheters, activation of relevant dwell positions and dosimetry, including optimization. Towards establishing effective methods for quality assurance of the optimized HDR surface mold planning calculations, we have compared their dosimetry to both a classical brachytherapy system and to one based on an analytical model of the applicator. The classical system yields an independent verification of the integrated activity used in the planning calculations, whereas the analytical model is used to evaluate depth dose dependence on mold size and optimization.