Auger electron therapy of glioblastoma using [I]5-iodo-2'-deoxyuridine and concomitant chemotherapy - Evaluation of a potential treatment strategy.

Introduction: Treatment of glioblastomas (GBM) using the Auger electron emitting compound [I]5-Iodo-2'-deoxyuridine ([I]I-UdR), combined with the thymidylate synthase inhibitor methotrexate (MTX) and concomitant chemotherapy with temozolomide (TMZ) has recently shown very promising therapeutic effects in vitro and in vivo in animals. The aim of the current study was to investigate if the therapeutic effects of this multimodal treatment strategy could be further increased by the thymidylate synthase inhibitor, 5-fluoro-2'-deoxyuridine (F-UdR), in comparison to MTX, and if the co-treatment should be given in a neoadjuvant or adjuvant setting.

Methods: A patient-derived GBM cancer stem cell (CSC)-enriched cell line, grown as neurospheres, was employed to evaluate DNA-incorporation of [I]I-UdR, determined by a DNA precipitation assay, using either pre-treatment or co-treatment with MTX or F-UdR.

Highly Effective Auger-Electron Therapy in an Orthotopic Glioblastoma Xenograft Model using Convection-Enhanced Delivery.

Glioblastoma, the most common and malignant primary brain tumor, always recurs after standard treatment. Therefore, promising new therapeutic approaches are needed. Short-range Auger-electron-emitters carry the ability of causing highly damaging radiation effects in cells.