Enhanced Delivery of Boronophenylalanine for Neutron Capture Therapy by Means of Intracarotid Injection and Blood-Brain Barrier Disruption
Autor: | Weilian Yang, David E. Carpenter, Joseph H. Goodman, Rolf F. Barth, Melvin L. Moeschberger |
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Rok vydání: | 1996 |
Předmět: |
Boron Compounds
inorganic chemicals Radiation-Sensitizing Agents medicine.medical_specialty Phenylalanine chemistry.chemical_element Blood–brain barrier Horseradish peroxidase chemistry.chemical_compound Internal medicine Glioma medicine.artery Tumor Cells Cultured medicine Animals Mannitol Tissue Distribution Common carotid artery Dominance Cerebral Boron Evans Blue biology Brain Neoplasms business.industry Brain Neutron Capture Therapy medicine.disease Rats Inbred F344 Rats Carotid Arteries Endocrinology medicine.anatomical_structure Injections Intra-Arterial chemistry Blood-Brain Barrier biology.protein Surgery Neurology (clinical) Nuclear medicine business Neoplasm Transplantation medicine.drug |
Zdroj: | Neurosurgery. 38:985-992 |
ISSN: | 1524-4040 0148-396X |
Popis: | There has been increasing interest in the possible use of boronophenylalanine as a capture agent for boron neutron capture therapy of brain tumors. The purpose of the present study was to determine whether the uptake of boronophenylalanine in F98 glioma-bearing rats could be enhanced by means of intracarotid (i.c.) injection with or without blood-brain barrier disruption (BBB-D). Glioma cells (10(5)) were stereotactically implanted into the right cerebral hemisphere of Fischer rats, and 12 days later, BBB-D was performed by infusing 25% mannitol (1.373 mOsmol/ml) into the right carotid artery and then immediately injecting L-boronophenylalanine (300 mg/kg of body weight) intracarotidly. The animals were killed 0.5, 1, 2.5, and 4 hours later, and the brains were removed for boron determination by direct current plasma atomic emission spectroscopy. BBB-D was assessed by the intravenous injection of Evans blue or horseradish peroxidase, and the barrier-disrupted hemispheres and tumors showed intense staining with each. The mean tumor boron concentration after i.c. injection and BBB-D was 34.8 +/- 6.8 micrograms/g at 2.5 hours compared with 20.3 +/- 6.2 micrograms/g after i.c. injection without BBB-D and 10.7 +/- 0.7 micrograms/g after intravenous injection. No significant differences in boron concentration in muscle, skin, and eye were observed among the different groups. Boron concentrations in the ipsilateral, disrupted hemisphere increased transiently but rapidly returned to background levels by 2.5 hours after BBB-D. The tumor:brain and tumor:blood ratios were 5.2 and 5.6, respectively, compared to 3.2 and 2.1 for intravenous injection groups at 2.5 hours. The present study is the first to show that BBB-D combined with i.c. injection can enhance the tumor uptake of boron compounds for boron neutron capture therapy. |
Databáze: | OpenAIRE |
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