title: [Effect of high-dose methotrexate on cerebral metabolic rate of glucose in rats and children with acute lymphoblastic leukemia].
abstract: For assessment of high-dose methotrexate (HD-MTX) neurotoxicity, regional cerebral metabolic rates of glucose (rCMRGlu) in rats and children with acute lymphoblastic leukemia were measured. rCMRGlu in rats receiving HD-MTX (300 or 600 mg/kg) was measured using 14C-deoxyglucose and autoradiographic technique. CMRGlu of the whole brain after HD-MTX was reduced by 31% on the average (p less than 0.01). CMRGlu of cerebral cortex was reduced more than that of white matter. Eight children with ALL (mean age 9.6 years) were studied using 18F-fluorodeoxyglucose and positron emission tomography before and after HD-MTX (200 mg/kg or 2,000 mg/M2) therapy. Although no patients clinically showed any neurological abnormalities during HD-MTX therapy, CMRGlu of the whole brain after HD-MTX was reduced by 21% on the average (p less than 0.05). Reduction rates of rCMRGlu after HD-MTX therapy were correlated with both total doses of intrathecal MTX (r = 0.717, p less than 0.05) and total doses of systemic HD-MTX (r = 0.784, p less than 0.05). The reduction rate of CMRGlu of cerebral cortex, particularly frontal and occipital cortex, was greater than either that of basal ganglia or white matter. It is suggested that measurement of rCMRGlu after HD-MTX is useful for detecting accumulated neurotoxicity of MTX.
authors.affiliation: Department of Pediatrics, Akita University, School of Medicine.
authors.forename: K
authors.initials: K
authors.lastname: Komatsu
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D005947:Glucose; D008727:Methotrexate