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.