{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T20:22:39Z","timestamp":1694636559501},"reference-count":53,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1984,5]]},"abstract":"\u2713 Diaziquone (also called \u201caziridinyl benzoquinone,\u201d 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 (14<\/jats:sup>C)-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 14<\/jats:sup>C-AZQ by intravenous infusion. Levels of chloroform (CHCl3<\/jats:sub>)-extractable 14<\/jats:sup>C (AZQ only) and total 14<\/jats:sup>C (AZQ and metabolites) were determined in serial samples of plasma and cerebrospinal fluid (CSF). At the end of the infusion time, total and CHCl3<\/jats:sub>-extractable 14<\/jats:sup>C 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<\/jats:sub>-extractable 14<\/jats:sup>C (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.<\/jats:p>\nComparison of right and left hemispheres following intra-arterial infusion showed a slightly higher concentration of 14<\/jats:sup>C in the ipsilateral (left) hemisphere, with concentrations (nmol\/gm) of CHCl3<\/jats:sub>-extractable 14<\/jats:sup>C\/total 14<\/jats:sup>C of 0.15\/0.87 on the left and 0.12\/0.65 on the right. Concentrations (nmol\/gm) of CHCl3<\/jats:sub>-extractable 14<\/jats:sup>C\/total 14<\/jats:sup>C 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.<\/jats:p>","DOI":"10.3171\/jns.1984.60.5.1005","type":"journal-article","created":{"date-parts":[[2009,5,8]],"date-time":"2009-05-08T18:33:32Z","timestamp":1241807612000},"page":"1005-1013","source":"Crossref","is-referenced-by-count":5,"title":["The pharmacology of diaziquone given in intravenous or intracarotid infusion to normal and intracranial tumor-bearing puppies"],"prefix":"10.3171","volume":"60","author":[{"given":"Merrill J.","family":"Egorin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edwin H.","family":"Bellis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Salcman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerry M.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James F.","family":"Spiegel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas R.","family":"Bachur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1754","reference":[{"key":"b1","series-title":"Proc Am Soc Clin Oncol","first-page":"148","article-title":"Phase II study of aziridinylbenzoquinone (AZQ) in patients with refractory small cell carcinoma of the lung.","volume":"1","author":"Aisner","year":"1982"},{"key":"b2","series-title":"Proc Am Soc Clin Oncol","first-page":"24","article-title":"A Phase II trial of AZQ (NSC 182986) in patients with recurrent primary or metastatic brain tumors.","volume":"1","author":"Aroney","year":"1982"},{"key":"b3","series-title":"Clin Pharmacol Ther","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1038\/clpt.1982.90","article-title":"Diaziquone, 2,5-diaziridinyl-3,6-biscarboethoxyamino-1,4-benzoquinone, plasma and cerebrospinal fluid kinetics.","volume":"31","author":"Bachur","year":"1982"},{"key":"b4","series-title":"Proc Am Assoc Cancer Res","first-page":"189","article-title":"Phase I evaluation of aziridinylbenzoquinone (NSC-182986) in a weekly i.v. schedule.","volume":"22","author":"Baker","year":"1981"},{"key":"b5","series-title":"Proc Am Soc Clin Oncol","first-page":"155","article-title":"Phase II evaluation of aziridinylbenzoquinone (AZQ) in the primary treatment of locally advanced or extensive non small cell lung cancer.","volume":"1","author":"Carey","year":"1982"},{"key":"b6","series-title":"Cancer Treat Rep","first-page":"31","article-title":"Intra-arterial infusion of anticancer drugs: theoretic aspects of drug delivery and review of responses.","volume":"64","author":"Chen","year":"1980"},{"key":"b7","series-title":"J Med Chem","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1021\/jm00233a010","article-title":"Potential central nervous system antitumor agents. 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