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Regional Measurements of Blood-to-Tissue Transport in Experimental RG-2 Rat Gliomas¹

Department of Neurology, Northwestern University, Evanston Hospital, Evanston, Illinois 60201 [D. R. G., J. F. P., J. M. F., N. A. V.]; Membrane Transport Section, Laboratory of Chemical Pharmacology, National Cancer Institute, NIH, Bethesda, Maryland 20205 [R. G. B.]; and Department of Pathology (Neuropathology), Duke University Medical Center, Durham, North Carolina 27710 [D. D. B.]

Regional measurements of blood-to-tissue transport were performed in transplanted RG-2 rat gliomas using [-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 µm 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.

¹ Supported in part by grants from the Boothroyd Foundation, Association for Brain Tumor Research, and the Richard Lilienfeld Memorial Fund.

² Recipient of USPHS Grant NS12745. To whom requests for reprints should be addressed, at Evanston Hospital, 2650 Ridge Ave., Evanston, Ill. 60201.

³ Recipient of USPHS Grant NS12745.

⁴ Recipient of USPHS Grant CA11898.

Received 8/23/82. Accepted 4/ 5/83.

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