caa a22 4500 469117168 CHVBK 20180323133128.0 cr unu---uuuuu 170328e19921001xx s 000 0 eng 10.1007/BF00177621 doi (NATIONALLICENCE)springer-10.1007/BF00177621 Intrathecal ACNU treatment of B16 melanoma leptomeningeal metastasis in a new athymic rat model [Elektronische Daten] [Martin Schabet, Petra Ohneseit, Rainer Buchholz, Lan Santo-Höltje, Heinz Schmidberger] Summary: To evaluate new cytotoxic drugs for intrathecal treatment we developed an experimental model of leptomeningeal metastasis by intracisternal injection of 104B16-F10 melanoma cells in nude rats. One hour in vitro incubation with 20 μg/ml ACNU (area under the drug concentration-time curve = 1200 μgxmin/ml) induced a 4-log kill of B16 melanoma cells. A single or repeated non-toxic dose of 1 mg/kg was injected into the cisterna magna of rats inoculated with tumor (area under the drug concentration-time curve assuming an even cerebrospinal fluid distribution > 7000 μgxmin/ml). Median survival free of symptoms was 16 days (range 14-27) for controls (n = 9) and 18 days (range 17-23) for rats treated with ACNU on day 4 (n = 9). Animals treated both on day 2 and 8 (n = 8) developed symptoms on day 21 (range 13-35). Neurological symptoms and neuropathological examination in animals with increased survival indicated local suppression of tumor growth in the cisterna magna but increased spinal seeding and mass growth. From these results and the available pharmacokinetic data on ACNU it is concluded that bolus injection of ACNU — although locally effective — is not a sufficient treatment of widespread leptomeningeal metastasis. An increased therapeutic efficacy might be achieved by ventriculolumbar perfusion. Kluwer Academic Publishers, 1992 leptomeningeal metastasis nationallicence meningeal carcinomatosis nationallicence B16 melanoma nationallicence intrathecal chemotherapy nationallicence ACNU nationallicence Schabet Martin Department of Neurology, University of Tübingen, 7400, Tübingen, Germany aut Ohneseit Petra Department of Radiotherapy, University of Tübingen, 7400, Tübingen, Germany aut Buchholz Rainer Department of Neurosurgery, University of Tübingen, 7400, Tübingen, Germany aut Santo-Höltje Lan Department of Radiotherapy, University of Tübingen, 7400, Tübingen, Germany aut Schmidberger Heinz Department of Radiotherapy, University of Tübingen, 7400, Tübingen, Germany aut Journal of Neuro-Oncology Kluwer Academic Publishers 14/2(1992-10-01), 169-175 0167-594X 14:2<169 1992 14 11060 https://doi.org/10.1007/BF00177621 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00177621 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Schabet Martin Department of Neurology, University of Tübingen, 7400, Tübingen, Germany aut NATIONALLICENCE 700 1- Ohneseit Petra Department of Radiotherapy, University of Tübingen, 7400, Tübingen, Germany aut NATIONALLICENCE 700 1- Buchholz Rainer Department of Neurosurgery, University of Tübingen, 7400, Tübingen, Germany aut NATIONALLICENCE 700 1- Santo-Höltje Lan Department of Radiotherapy, University of Tübingen, 7400, Tübingen, Germany aut NATIONALLICENCE 700 1- Schmidberger Heinz Department of Radiotherapy, University of Tübingen, 7400, Tübingen, Germany aut NATIONALLICENCE 773 0- Journal of Neuro-Oncology Kluwer Academic Publishers 14/2(1992-10-01), 169-175 0167-594X 14:2<169 1992 14 11060 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer