A comparison of oral and intravenous pimonidazole in canine tumors using intravenous CCI-103F as a control hypoxia marker.
OBJECTIVE
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
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.
Kleiter
Miriam M
MM
College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27514-7512, USA.
Thrall
Donald E
DE
Malarkey
David E
DE
Ji
Xiaoshen
X
Lee
David Y W
DY
Chou
Shu-Chuan
SC
Raleigh
James A
JA
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D015687:Cell Hypoxia; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D005240:Feasibility Studies; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D009369:Neoplasms / Q000378:metabolism / Q000662:veterinary*; D009593:Nitroimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005466:Fluorocarbons
D009593:Nitroimidazoles; C049948:CCI 103F; D005466:Fluorocarbons; C033815:pimonidazole