[ACNU delivery to malignant glioma tissue by osmotic blood brain barrier modification with intracarotid infusion of hyperosmoral mannitol].

Drug delivery to the tumor has been one of the major subjects in the field of brain tumor chemotherapy because of blood brain barrier. Recent studies including quantitative autoradiographic studies revealed that blood brain barrier is present and intact in the brain adjacent to tumor where viable tumor cells are infiltrating, and also in the tumors which are early in the development. In 1972 Rapoport et al demonstrated that it is possible to transiently and reversibly open the blood brain barrier by an intracarotid infusion of a hyperosmoral solution. This technique is found to increase cerebrovascular permeability to chemotherapeutic agents. Six cases of glioma, including 4 astrocytoma grade 4, 1 astrocytoma grade 3, 1 astrocytoma grade 2, were treated during operation with intracarotid infusion of ACNU 100 mg/body/5 min. (1.3-2.2 mg/kg) following intracarotid infusion of 20% mannitol 200 ml (1.3-1.6 ml/sec) through the catheter in the internal carotid artery set preoperatively, and ACNU concentration in tumor tissues and blood were measured at 5, 10, 15, 20, 25, 30, 40, 60 minutes after that. On every case mannitol contrast enhancement CT was studied by the intracarotid infusion of 60% conray 100 ml/5 min. following the intracarotid infusion of 20% mannitol 200 ml comparing with contrast enhancement CT and plain CT. Maximum ACNU concentrations in blood were 2.12-4.12 micrograms/ml (mean 3.1 +/- 0.74) at 5 min. after the intraarterial administration of mannitol and ACNU on every case. At 20 min. following the administration ACNU levels were decreased to half level (mean 1.49 +/- 0.42 microgram/ml) and 0.58 +/- 0.18 microgram/ml at 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)