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Regional measurements of blood-to-tissue transport were performed in transplanted RG-2 rat gliomas using [alpha- 14C]aminoisobutyric acid (AIB), quantitative autoradiography, and equations to express a unidirectional transfer constant. Thirty-eight intracranial tumors in ten rats were analyzed according to location; 23 intraparenchymal tumors, eight meningeal tumors, six fourth-ventricular tumors, and one third-ventricular tumor were studied. Except for the small third-ventricular tumor, the transfer constant (K) for AIB was similar in all groups and ranged from 0.031 to 0.038 ml/g/min. Within individual tumors, regional variation of K was also small, although some local variation could be correlated with histological features. The K for AIB decreased in brain around tumor and, at a distance of 300 microns from tumor edge, had returned to values similar to those of normal cortex (0.002 ml/g/min). An average extraction fraction (E) of 0.09 was calculated for AIB in the RG-2 tumors. The low E suggests that delivery of water-soluble chemotherapeutic drugs to RG-2 tumors should be limited more by capillary permeability or surface area than by blood flow. RG-2 is an ideal experimental tumor with which to test drug delivery and the methods that attempt to increase drug delivery in brain tumors. |
