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Low-energy electrons transform the nimorazole molecule into a radiosensitiser.
Nat Commun
June 2019
Institut für Ionenphysik und Angewandte Physik and Center for Biomolecular Sciences Innsbruck, Leopold-Franzens Universität Innsbruck, Technikerstrasse 25, A-6020, Innsbruck, Austria.
While matter is irradiated with highly-energetic particles, it may become chemically modified. Thereby, the reactions of free low-energy electrons (LEEs) formed as secondary particles play an important role. It is unknown to what degree and by which mechanism LEEs contribute to the action of electron-affinic radiosensitisers applied in radiotherapy of hypoxic tumours.
View Article and Find Full Text PDFOvercoming Radioresistance: Small Molecule Radiosensitisers and Hypoxia-activated Prodrugs.
Clin Oncol (R Coll Radiol)
May 2019
Auckland Cancer Society Research Centre, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand. Electronic address:
The role of hypoxia in radiation resistance is well established and many approaches to overcome hypoxia in tumours have been explored, with variable success. Two small molecule strategies for targeting hypoxia have dominated preclinical and clinical efforts. One approach has been the use of electron-affinic nitroheterocycles as oxygen-mimetic sensitisers.
View Article and Find Full Text PDFPutative electron-affinic radiosensitizers and markers of hypoxic tissue: Synthesis and preliminary in vitro biological characterization of C3-amino-substituted benzotriazine dioxides (BTDOs).
Eur J Med Chem
March 2019
Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, 11560 University Avenue Edmonton, Alberta, T6G 1Z2, Canada. Electronic address:
Introduction: The redox characteristics of 1,2,4-benzotriazine-1,4-dioxides (BTDOs) make them potential radiosensitizing agents for hypoxic cells in solid human cancers. Tirapazamine (TPZ) is the most clinically tested BTDO radiosensitizer, despite its toxicity at effective doses. To date, no BTDOs have been developed as diagnostic markers of tissue hypoxia.
View Article and Find Full Text PDFElectron-Induced Dissociation of the Potential Radiosensitizer 5-Selenocyanato-2'-deoxyuridine.
J Phys Chem B
February 2019
Institut für Ionenphysik und Angewandte Physik and Center for Biomolecular Sciences Innsbruck , Leopold-Franzens Universität Innsbruck, Technikerstrasse 25 , A-6020 Innsbruck , Austria.
5-Selenocyanato-2'-deoxyuridine (SeCNdU) is a recently proposed radiosensitizer based on 2'-deoxyuridine (dU) with the electron-affinic selenocyanato (-SeCN) side group attached at the C5 position of uracil. Since electron interaction processes may be an important source of DNA damage by ionizing radiation, we have studied low-energy dissociative electron attachment to SeCNdU in the gas phase. Negative ion formation has been obtained by means of mass spectrometry, where a rich fragmentation pattern is observed even at ∼0 eV.
View Article and Find Full Text PDFThe chemistry and radiochemistry of hypoxia-specific, radiohalogenated nitroaromatic imaging probes.
Semin Nucl Med
March 2015
Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
Hypoxia is prevalent in many solid tumors. Hypoxic tumors tend to exhibit rapid growth and aberrant vasculature, which lead to oxygen (O2) depletion and impaired drug delivery. The reductive environment in hypoxic tumors alters cellular metabolism, which can trigger transcriptional responses; induce genetic alterations; promote invasion, metastasis, resistance to radiotherapy and chemotherapy, tumor progression, and recurrence; and leads to poor local control and reduced survival rates.
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