Efficient Protocol for the Identification of Hypoxic Cell Radiosensitisers.
An evolution in radiotherapy practice is leading to greater use of stereotactic body radiotherapy (SBRT), raising the prospect of increased hypoxic cell radioresistance. New clinical interest in nitroimidazole radiosensitisers, combined with appropriate biomarkers, signals a revival for radiosensitisers in the context of SBRT. Our interest in modifiers of radiation therapy led us to revisit this area and we have identified a new class of nitroimidazole radiosensitiser. We have developed an abbreviated screening protocol suitable for an academic drug discovery laboratory which allows expeditious triage of compounds with poor physicochemical and in vitro properties and combines in vitro radiosensitisation data with tumour pharmacokinetic data to efficiently select candidates for further evaluation.
Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Cho Rong
CR
Hong
Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Jingli
J
Wang
Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Kevin O
KO
Hicks
Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand. m.hay@auckland.ac.nz.
Michael P
MP
Hay
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D008819:Mice, Nude; D009369:Neoplasms / Q000473:pathology; D011838:Radiation-Sensitizing Agents / Q000032:analysis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D016634:Radiosurgery
D015415:Biomarkers; D011838:Radiation-Sensitizing Agents
Drug discovery; Hypoxia; Nitroimidazole; Radiosensitiser