title: 111Indium-diethylenetriamine pentaacetic acid cerebrospinal fluid flow studies predict distribution of intrathecally administered chemotherapy and outcome in patients with leptomeningeal metastases.
abstract: Abnormal CSF flow can impair the distribution of intrathecally administered drugs. We examined the relationship between 111indium-diethylenetriamine pentaacetic acid (111In-DTPA) CSF flow studies and methotrexate levels in ventricular and lumbar CSF and correlated these findings with outcome in patients with leptomeningeal metastases (LM). Seven men and 10 women with LM (10 solid tumors, 6 lymphoma, 1 leukemia) received 12 mg methotrexate and 0.5 mCi 111In-DTPA by intra-Ommaya injection; images were obtained immediately and after 4, 24, and 48 hours. Ventricular and lumbar CSF methotrexate and radioactivity levels were measured 6 hours after injection. Thirteen patients had abnormal CSF flow studies, 9 with multiple sites of obstruction. CSF flow obstruction was observed at ventricular outlets in 13 patients, cerebral convexities in 9 and in the spine in 2. With one exception, all obstructions were explicable by tumor deposits on MRIs. For all patients, ventricular and lumbar methotrexate and radioactivity levels correlated closely. Three patients with a normal CSF flow study are alive at 15+, 7.5+, and 3.9+ months from treatment. Of 12 with abnormal CSF flow studies, 11 are dead a median of 2 months from diagnosis. Two patients had diffusely delayed flow studies and both developed methotrexate leukoencephalopathy. CSF flow studies using 111In-DTPA reliably predict distribution of intrathecal methotrexate. Abnormal flow studies correlate with structural abnormalities, are an unfavorable prognostic factor, and may predict intrathecal chemotherapy toxicity.
authors.affiliation: Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: W P
authors.initials: WP
authors.lastname: Mason
authors.forename: S D
authors.initials: SD
authors.lastname: Yeh
authors.forename: L M
authors.initials: LM
authors.lastname: DeAngelis
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics; D007278:Injections, Spinal; D008279:Magnetic Resonance Imaging; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D004369:Pentetic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D004369:Pentetic Acid; D008727:Methotrexate