|
|
|
|
Validation of 64Cu-ATSM damaging DNA via high-LET Auger electron emission
|
|
|
|
|
|
|
|
نویسنده
|
mcmillan d.d. ,maeda j. ,bell j.j. ,genet m.d. ,phoonswadi g. ,mann k.a. ,kraft s.l. ,kitamura h. ,fujimori a. ,yoshii y. ,furukawa t. ,fujibayashi y. ,kato t.a.
|
|
منبع
|
journal of radiation research - 2015 - دوره : 56 - شماره : 5 - صفحه:784 -791
|
|
چکیده
|
Radioactive copper (ii) (diacetyl-bis n4-methylthiosemicarbazone) (cu-atsm) isotopes were originally developed for the imaging of hypoxia in tumors. because the decay of a 64cu atom is emitting not only positrons but also auger electrons,this radionuclide has great potential as a theranostic agent. however,the success of 64cu-atsm internal radiation therapy would depend on the contribution of auger electrons to tumor cell killing. therefore,we designed a cell culture system to define the contributions to cell death from auger electrons to support or refute our hypothesis that the majority of cell death from 64cu-atsm is a result of high-let auger electrons and not positrons or other low-let radiation. chinese hamster ovary (cho) wild type and dna repair-deficient xrs5 cells were exposed to 64cu-atsm during hypoxic conditions. surviving fractions were compared with those surviving gamma-radiation,low-let hadron radiation,and high-let heavy ion exposure. the ratio of the d10 values (doses required to achieve 10% cell survival) between cho wild type and xrs5 cells suggested that 64cu-atsm toxicity is similar to that of high-let carbon ion radiation (70 kev/μm). γh2ax foci assays confirmed dna double-strand breaks and cluster damage by high-let auger electrons from 64cu decay,and complex types of chromosomal aberrations typical of high-let radiation were observed after 64cu-atsm exposure. the majority of cell death was caused by high-let radiation. this work provides strong evidence that 64cu-atsm damages dna via high-let auger electrons,supporting further study and consideration of 64cu-atsm as a cancer treatment modality for hypoxic tumors. © 2015 the author 2015. published by oxford university press on behalf of the japan radiation research society and japanese society for radiation oncology.
|
|
کلیدواژه
|
64Cu-ATSM; auger electron; CHO; DNA double strand break; high LET
|
|
آدرس
|
department of environmental and radiological health sciences,colorado state university,fort collins,co 80523, United States, department of environmental and radiological health sciences,colorado state university,fort collins,co 80523, United States, department of environmental and radiological health sciences,colorado state university,fort collins,co 80523, United States, department of environmental and radiological health sciences,colorado state university,fort collins,co 80523, United States, department of environmental and radiological health sciences,colorado state university,fort collins,co 80523, United States, department of environmental and radiological health sciences,colorado state university,fort collins,co 80523, United States, department of environmental and radiological health sciences,colorado state university,fort collins,co 80523, United States, research development and support center,national institute of radiological sciences,4-9-1 anagawa,inage,chiba,263-8555, Japan, research center for radiation protection,national institute of radiological sciences,4-9-1 anagawa,inage,chiba,263-8555, Japan, molecular imaging center,national institute of radiological sciences,4-9-1 anagawa,inage,chiba,263-8555, Japan, molecular imaging center,national institute of radiological sciences,4-9-1 anagawa,inage,chiba,263-8555, Japan, molecular imaging center,national institute of radiological sciences,4-9-1 anagawa,inage,chiba,263-8555, Japan, department of environmental and radiological health sciences,colorado state university,fort collins,co 80523, United States
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|