(111)INDIUM-DIETHYLENETRIAMINE PENTAACETIC ACID CEREBROSPINAL-FLUID FLOW STUDIES PREDICT DISTRIBUTION OF INTRATHECALLY ADMINISTERED CHEMOTHERAPY AND OUTCOME IN PATIENTS WITH LEPTOMENINGEAL METASTASES

Abnormal CSF now can impair the distribution of intrathecally administ ered drugs. We examined the relationship between (111)indium-diethylen etriamine pentaacetic acid (In-111-DTPA) CSF flow studies and methotre xate levels in ventricular and lumbar CSF and correlated these finding s with outcome in patients with leptomeningeal metastases (LM). Seven men and 10 women with LM (10 solid tumors, 6 lymphoma, 1 leukemia) rec eived 12 mg methotrexate and 0.5 mCi In-111-DTPA by intra-Ommaya injec tion; 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 f low studies, 9 with multiple sites of obstruction. CSF flow obstructio n was observed at ventricular outlets in 13 patients, cerebral convexi ties in 9, and in the spine in 2. With one exception, all obstructions were explicable by tumor deposits on MRIs. For all patients, ventricu lar and lumbar methotrexate and radioactivity levels correlated closel y. 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 dif fusely delayed flow studies and both developed methotrexate leukoencep halopathy. CSF now studies using In-111-DTPA reliably predict distribu tion of intrathecal methotrexate. Abnormal flow studies correlate with structural abnormalities, are an unfavorable prognostic factor, and m ay predict intrathecal chemotherapy toxicity.