The effect of dexamethasone on the uptake of p-boronophenylalanine in the rat brain and intracranial 9L gliosarcoma.
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 3mg/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 1.5mg/kg at 17 h and 1h prior to BPA injection for a total dose of 3mg 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; approximately 59 mg (10)B/kg). In all groups, rats were euthanized at 3h after BPA injection. Administration of the steroid had an effect on tumor weight, which decreased to approximately 78% (p > 0.05) of the control weight in the low-dose DEX group, and approximately 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 microg/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 microg/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 approximately 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.
Normal Tissue Radiobiological Research Group, Research Institute, Churchill Hospital, Oxford OX3 7LJ, UK.
G M
GM
Morris
P L
PL
Micca
J A
JA
Coderre
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001896:Boron Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016754:Boron Neutron Capture Therapy; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D001932:Brain Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D003907:Dexamethasone / Q000494:pharmacology*; D018316:Gliosarcoma / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344
C436045:4-dihydroxyborylphenylalanine; D001896:Boron Compounds; D010649:Phenylalanine; D003907:Dexamethasone