The effect of graded hypertonic intracarotid infusions on drug delivery to experimental RG-2 gliomas.
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 water-soluble 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.
D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism*; D006982:Hypertonic Solutions / Q000494:pharmacology*; D007261:Infusions, Intra-Arterial; D008297:Male; D008954:Models, Biological; D051381:Rats; D011916:Rats, Inbred F344
D000621:Aminoisobutyric Acids; D000970:Antineoplastic Agents; D006982:Hypertonic Solutions; C100049:2-aminoisobutyric acid