Monitoring of methotrexate delivery in patients with malignant brain tumors after osmotic blood-brain barrier disruption

Abstract

Reversible transient osmotic blood-brain barrier disruption was used to increase drug delivery to the brain. Methotrexate was administered 33 times to six patients with brain tumors after barrier disruption. No permanent complications were seen. Serial enhanced computed tomographic (CT) scans and quantification by CT tomographic number indicated that disruption increased drug delivery to the tumor and immediate surrounding brain. Neuroradiologic evaluation showed that drug in the tumor persisted longer after barrier disruption than when delivered without disruption. The concentration of methotrexate in spinal fluid did not correlate with the degree of barrier disruption measured by CT and radionuclide scans. In one patient an anatomic variation in the circle of Willis resulted in barrier disruption extending into the posterior fossa without ill effect. Osmotic blood-brain barrier disruption appears to be a safe procedure in man, able to increase drug delivery to both malignant brain tumors and surrounding brain parenchyma.