HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nakagawa, H. Articles by Blasberg, R. G. Search for Related Content PubMed PubMed Citation Articles by Nakagawa, H. Articles by Blasberg, R. G.

The effect of graded hypertonic intracarotid infusions on drug delivery to experimental RG-2 gliomas

From the Laboratory of Medicinal Chemistry and Pharmacology (Drs. Nakagawa and Blasberg), DTP, Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda. MD, and the Department of Neurology (Dr. Groothuis), Northwestern University, Evanston Hospital, Evanston. IL.

The RG-2 brain tumor model was used to determine whether unidirectional transport of alpha-aminoisobutyric acid (AIB) into brain and tumor tissue was increased after an intracarotid infusion of one of six different hypertonic solutions of L-arabinose. Intracarotid infusion of hypertonic solutions that have been reported as subthreshold for normal brain were used to determine whether they would selectively increase blood-to-tissue transport in brain tumors. No increase in the transport rate constant (K) across RG-2 tumor capillaries resulted from the infusion of 0.8- to 1.4-osm solutions. Infusions of 1.6- and 1.8-osm solutions were also performed, and blood-to-tissue transport was measured under conditions that produce maximum blood-brain-barrier disruption; however, no increase in the transport rate across tumor capillaries was measured. In brain regions surrounding the tumor, there was a trend toward increasing K values associated with increasing osmolality of the infusate, but the magnitude of this increase was small. There was a progressive increase in the K of tumor-free brain regions. This increase correlated with increasing osmolality of the infusate (0.8 to 1.8 osm). We conclude that intracarotid infusion of hypertonic solutions of L-arabinose does not increase the rate of delivery of watersoluble drugs to experimental RG-2 brain tumors. In this situation, the use of hypertonic infusions may be counterproductive and result in a greater delivery to and exposure of surrounding and normal brain tissue to levels of chemotherapeutic drugs which are potentially neurotoxic.

Address correspondence and reprint requests to Dr. Blasberg, Nuclear Medicine Department, National Institutes of Health, Building 10, Room 1C401, Bethesda, MD 20205.

Presented in part at the thirty-fifth annual meeting of the American Academy of Neurology, San Diego, CA, April 1983. [Nakagawa H, Groothuis DP, Blasberg RG. Failure of intracarotid hyperosmolal infusion to increase brain tumor capillary permeability. Abstract. Neurology (Cleveland) 1983;33(Supp12):108].

Accepted for publication March 26, 1984

This article has been cited by other articles:

				D. R. Groothuis The blood-brain and blood-tumor barriers: A review of strategies for increasing drug delivery Neuro-oncol, January 1, 2000; 2(1): 45 - 59. [Abstract] [PDF]

				P. Molnar, I. Fekete, K. E. Schlageter, G. D. Lapin, and D. R. Groothuis Absence of Host-Site Influence on Angiogenesis, Blood Flow, and Permeability in Transplanted RG-2 Gliomas Drug Metab. Dispos., September 1, 1999; 27(9): 1085 - 1091. [Abstract] [Full Text]