Diaziquone (also called "aziridinyl
benzoquinone," or
AZQ), an
antitumor drug designed to penetrate the blood-brain barrier, has demonstrated activity against central nervous system (
CNS) neoplasms. Four-hour infusions of
carbon-14 (14C)-labeled
AZQ (0.8 mg/kg) were given via the left common carotid artery or left brachial vein to two groups of puppies. A third group, harboring a transplantable canine
glioma, received 14C-AZQ by
intravenous infusion. Levels of
chloroform (CHCl3)-extractable 14C (
AZQ only) and total 14C (
AZQ and metabolites) were determined in serial samples of plasma and cerebrospinal fluid (CSF). At the end of the infusion time, total and CHCl3-extractable 14C levels were determined in brain and
tumor.
Intra-arterial infusion of
AZQ caused no histological abnormalities in the retina or brain. For the
intravenous infusion group, the concentrations of CHCl3-extractable 14C (in nmol/ml or nmol/gm) were 0.68, 0.35, and 0.84 for plasma, brain, and CSF, respectively. For the
intra-arterial infusion group, the concentrations were 0.25, 0.13, and 0.32 for plasma, brain, and CSF, respectively. Comparison of right and left hemispheres following
intra-arterial infusion showed a slightly higher concentration of 14C in the ipsilateral (left) hemisphere, with concentrations (nmol/gm) of CHCl3-extractable 14C/total of 14C of 0.15/0.87 on the left and 0.12/0.65 on the right. Concentrations (nmol/gm) of CHCl3-extractable 14C/total 14C in brain and
tumor were 0.60/1.24 and 0.58/1.65, respectively. In
tumor-bearing animals,
tumor and surrounding brain contained similar concentrations of
AZQ, but there were higher concentrations of metabolites in
tumor. This may reflect different metabolism of
AZQ within brain and
tumor or different permeability to metabolites. This study revealed that
AZQ enters the CNS and
brain-tumor tissue in substantial concentrations and that there is no significant advantage to intracarotid infusion of
AZQ.