RG2 Rat Glioma Model: Influence of the Blood-Brain Barrier on Biodistribution of Boronsulfhydryl
The accumulation of borocaptate sodium (BSH) and other boronated molecules in brain tumors and normal brain is dependent, in part, upon the blood-brain barrier (BBB). Current investigations into the biodistribution of various boron carriers in animals and humans are done on intact tumors not subjected to previous surgery, whereas actual Boron Neutron Capture Therapy (BNCT) takes place shortly after surgical debulking (Hatanaka et al, 1992). The RG2 intracerebrally transplantable rat glioma (Krajewski et al, 1986) was used to develop an experimental model which would allow the simulation of the situation in patients undergoing BNCT 2 to 4 weeks after craniotomy for gross tumor resection. Surgical removal of the transplanted tumor was therefore attempted under general anesthesia approximately 1 week prior to the BSH administration, and the animals were allowed to recover. This model was established to study the tissue boron concentration in minute samples after intravenous administration of BSH, and its relationship to the degree of disrupture of the BBB by the intact tumor, by surgery alone, and by the combined effect of tumor and surgery. The BBB was assessed by the use of intravenous sodium fluorescein (SF). The model should permit the quantitative investigation of the interference of steroids and mannitol with SF and BSH biodistribution. These two drugs are commonly used in clinical practice and are known to influence the BBB. This work should result in the establishment of base line values concerning the behaviour of BSH in a biological system close to clinical reality which would allow a rapid and quantitative comparison of BSH with other boronated molecules.
KeywordsBoron Concentration Boron Neutron Capture Therapy Sodium Fluorescein Surgical Debulking Intact Tumor
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