Radiobiological effects of hypoxia-dependent uptake of 64Cu-ATSM: enhanced DNA damage and cytotoxicity in hypoxic cells

Abstract

The results support a model in which hypoxia-enhanced uptake of radiotoxic (64)Cu induces sufficient DNA damage and toxicity to overcome the documented radioresistance in hypoxic MCF-7 cells. This suggests that (64)Cu-ATSM and related complexes have potential for targeted radionuclide therapy of hypoxic tumours.

Demonstration of the retention of 64Cu-ATSM in cardiac myocytes using a novel incubation chamber for screening hypoxia-dependent radiotracers

“…Temperature and pO 2 were recorded using an Oxylab pO 2 system equipped with a combined pO 2 /temperature sensor (Oxford Optronix). 64 Cu-ATSM production 64 Cu was produced at the Clinical PET Centre, St Thomas' Hospital, London, UK, as previously reported [15] and was used to synthesize 64 Cu-ATSM [16,17]. ATSM was dissolved in dimethyl sulfoxide (1 mg/ml), and the ligand solution (10 ml) and 30 MBq of 64 CuCl (aq) were mixed and made up to a final volume of 1 ml with ultrapure water.…”

Positron emission tomography to assess hypoxia and perfusion in lung cancer

“…The short-lived radionuclides can be used for sequential measurements, whereas radionuclides with longer half lives do Table 2 for full names. Lewis et al [133] , Yuan et al [134] , Kersemans et al [135] , Matsumoto et al [136] Ballegeer et al [137] , Bowen et al [138] , Lewis et al [133] , Myerson et al [139] , O'Donoghue et al [72] Ballegeer et al [137] , Hansen et al [140] , Matsumoto et al [136] , McCall et al [66] , O'Donoghue et al [72] , Oh et al [74] , Yuan et al [134] Grigsby et al [141] , Tateishi et al [142] , Valtorta et al [143] , Weeks et al [144] Dence et al [145] , Kersemans et al [135] , Lewis et al [146] , Matsumoto et al [136] , O'Donoghue et al [72] Dehdashti et al [86] , Lohith et al [67] , Wong et al [80] , Zhang et al [81] Chao et al [147] , Dehdashti et al [148] , Dehdashti et al [149] , Dietz et al [150] , Grassi et al [151] , Grigsby et al [141] , Kositwattanarerk et al [152] , Laforest et al [153] , Lewis et al [154] , Minagawa et al [155] , Nyflot et al [156] [ Mahy et al [158] , Mahy et al …”

Applications of “Hot” and “Cold” Bis(thiosemicarbazonato) Metal Complexes in Multimodal Imaging

“…The use of 64 CuATSM in therapy has been revealed to provide improved cytotoxicity and DNA damage under hypoxia. [109] However, some results have highlighted that CuATSM undergoes a complex uptake mechanism in vitro and in vivo, and its application for the imaging of tumors seems not to be universal. Regarding therapeutic applications, the optimization of the common 64 CuATSM needs to be undertaken.…”