PURPOSE: Pimonidazole HCl is widely used in immunohistochemical analyses of hypoxia in normal and malignant tissues. The present study investigates oral administration as a means of minimizing invasiveness. METHODS AND MATERIALS: Twelve dogs with confirmed malignancy received 0.5 g/m2 of pimonidazole HCl: 6 by mouth and 6 by i.v. infusion. All dogs received i.v. CCI-103F as a control. Plasma levels of pimonidazole, pimonidazole N-oxide, and CCI-103F were measured. Tumor biopsies were formalin fixed, paraffin embedded, sectioned, immunostained, and analyzed for pimonidazole and CCI-103F binding. pH dependence for pimonidazole and CCI-103F binding was studied in vitro. RESULTS: Pimonidazole and CCI-103F binding in carcinomas and sarcomas was strongly correlated for both oral and i.v. pimonidazole HCl (r2=0.97). On average, the extent of pimonidazole binding exceeded that for CCI-103F by a factor of approximately 1.2, with the factor ranging from 1.0 to 1.65. Binding of both markers was pH dependent, but pimonidazole binding was greater at all values of pH. CONCLUSIONS: Oral pimonidazole HCl is effective as a hypoxia marker in spontaneously arising canine tumors. Selective cellular uptake and concomitant higher levels of binding in regions of hypoxia at the high end of pH gradients might account for the greater extent of pimonidazole binding.
PURPOSE:Pimonidazole HCl is widely used in immunohistochemical analyses of hypoxia in normal and malignant tissues. The present study investigates oral administration as a means of minimizing invasiveness. METHODS AND MATERIALS: Twelve dogs with confirmed malignancy received 0.5 g/m2 of pimonidazole HCl: 6 by mouth and 6 by i.v. infusion. All dogs received i.v. CCI-103F as a control. Plasma levels of pimonidazole, pimonidazole N-oxide, and CCI-103F were measured. Tumor biopsies were formalin fixed, paraffin embedded, sectioned, immunostained, and analyzed for pimonidazole and CCI-103F binding. pH dependence for pimonidazole and CCI-103F binding was studied in vitro. RESULTS:Pimonidazole and CCI-103F binding in carcinomas and sarcomas was strongly correlated for both oral and i.v. pimonidazole HCl (r2=0.97). On average, the extent of pimonidazole binding exceeded that for CCI-103F by a factor of approximately 1.2, with the factor ranging from 1.0 to 1.65. Binding of both markers was pH dependent, but pimonidazole binding was greater at all values of pH. CONCLUSIONS: Oral pimonidazole HCl is effective as a hypoxia marker in spontaneously arising caninetumors. Selective cellular uptake and concomitant higher levels of binding in regions of hypoxia at the high end of pH gradients might account for the greater extent of pimonidazole binding.
Authors: Nerissa Therese Viola-Villegas; Sean D Carlin; Ellen Ackerstaff; Kuntal K Sevak; Vadim Divilov; Inna Serganova; Natalia Kruchevsky; Michael Anderson; Ronald G Blasberg; Oleg A Andreev; Donald M Engelman; Jason A Koutcher; Yana K Reshetnyak; Jason S Lewis Journal: Proc Natl Acad Sci U S A Date: 2014-05-01 Impact factor: 11.205
Authors: Vishnu Chintalgattu; Di Ai; Robert R Langley; Jianhu Zhang; James A Bankson; Tiffany L Shih; Anilkumar K Reddy; Kevin R Coombes; Iyad N Daher; Shibani Pati; Shalin S Patel; Jennifer S Pocius; George E Taffet; L Maximillian Buja; Mark L Entman; Aarif Y Khakoo Journal: J Clin Invest Date: 2010-01-11 Impact factor: 14.808
Authors: Elizabeth A Ballegeer; Nicole J Madrill; Kevin L Berger; Dalen W Agnew; Elizabeth A McNiel Journal: BMC Cancer Date: 2013-04-30 Impact factor: 4.430