The effect of dexamethasone on the uptake of p-boronophenylalanine in the rat brain and intracranial 9L gliosarcoma

Abstract

The steroid dexamethasone sodium phosphate (DEX) is routinely used to treat edema in brain tumor patients. The objective of the present study was to evaluate the effects of DEX on the uptake of boronophenylalanine (BPA) using the rat 9L gliosarcoma tumor model and surrounding brain tissue. Two steroid dosage protocols were used. The high-dose DEX protocol involved five 3 mg/kg intraperitoneal injections at 47, 35, 23, 11 and 1 h prior to the administration of the BPA for a total dose of 15 mg DEX/kg rat. The low-dose DEX administration protocol involved two doses of 1.5 mg/kg at 17 h and 1 h prior to BPA injection for a total dose of 3 mg DEX/kg rat. The control animals received no pretreatment, prior to the administration of BPA. Seventeen days after tumor implantation, rats were injected i.p. with 0.014 ml/g body weight BPA solution (1200 mg BPA/kg; ∼59 mg 10B/kg). In all groups, rats were euthanized at 3 h after BPA injection. Administration of the steroid had an effect on tumor weight, which decreased to ∼78% ( p>0.05) of the control weight in the low-dose DEX group, and ∼48% ( p<0.001) of the control weight in the high-dose DEX group. At 3 h after the administration of BPA, the concentration of boron in tumor was comparable ( p>0.1) in the control and high-dose DEX groups. The lowest mean value (73.8±1.6 μg/g) was obtained in the low-dose DEX group. This was significantly lower ( p>0.02) than the tumor boron contents in the high-dose DEX and control groups, which were 81.1±1.9 and 79.9±1.7 μg/g, respectively. Tumor:blood boron partition ratios for the control, low- and high-dose DEX groups were 2.3, 2.3 and 2.5, respectively. Boron concentrations were also measured in the normal brain and in the zone of brain adjacent to the tumor exhibiting edema. Although treatment with DEX had no appreciable effect on boron uptake in the normal brain of the rat, after the administration of BPA, it did impact on the boron levels in the zone of peritumoral edema. After the high-dose DEX administration protocol, boron levels in the zone of edema were reduced by ∼14% ( p<0.02). This finding suggests that BPA targeting of tumor cells in the peritumoral zone could be compromised by DEX. These cells appear to play a critical role in tumor recurrence after BNCT or conventional radiotherapy.