ABSTRACT
We studied the uptake of boron after 100 mg/kg BPA infusion in three meningioma and five schwannoma patients as a pre-BNCT feasibility study. With average tumour-to-whole blood boron concentrations of 2.5, we discuss why BNCT could, and probably should, be developed to treat severe forms of the studied tumours. However, analysing 72 tumour and 250 blood samples yielded another finding: the plasma-to-whole blood boron concentrations varied with time, suggesting that the assumed constant boron ratio of 1:1 between normal brain tissue and whole blood deserves re-assessment.
Subject(s)
Boron Compounds/administration & dosage , Boron Neutron Capture Therapy , Boron/pharmacokinetics , Brain Neoplasms/radiotherapy , Fructose/administration & dosage , Meningioma/radiotherapy , Neurilemmoma/radiotherapy , Phenylalanine/analogs & derivatives , Adult , Aged , Feasibility Studies , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Phenylalanine/administration & dosage , Tissue Distribution , Young AdultABSTRACT
A large, rapidly progressing, unresectable undifferentiated sinonasal head and neck carcinoma regressed rapidly following single fraction boron neutron capture therapy (BNCT). The main toxicity consisted of mucositis lasting for a few days. The quality of life improved and was excellent until tumour recurrence 6 months after the date of BNCT.
Subject(s)
Boron Neutron Capture Therapy , Carcinoma/radiotherapy , Paranasal Sinus Neoplasms/radiotherapy , Adult , Humans , Male , Mucous Membrane/pathology , Quality of Life , Stomatitis/etiology , Treatment OutcomeABSTRACT
Boron neutron capture therapy (BNCT) is an experimental therapeutic modality combining a boron pharmaceutical with neutron irradiation. 4-Dihydroxyborylphenylalanine (L-BPA) synthesised via the asymmetric pathway by Malan and Morin [Synlett. 167-168 (1996)] was developed to be the boron containing pharmaceutical in the first series of Finnish BNCT clinical trials. The final product was >98.5% chemically pure L-BPA with L-phenylalanine and L-tyrosine as the residual impurities. The solubility of L-BPA was enhanced by complex formation with fructose (BPA-F). The pH and osmolarity of the BPA-F preparation is in the physiological range. Careful attention was given to the pharmaceutical quality of the BPA-F preparations. Prior to starting clinical trials the acute toxicity of L-BPA was studied in male albino Sprague-Dawley rats. In accordance with earlier studies no adverse effects were observed. After completion of the development work L-BPA solution was administered to brain tumour patients in conjunction with clinical studies for development and testing of BPA-based BNCT. No clinically significant adverse events attributable to the L-BPA i.v. infusions were observed. We conclude that our synthesis development, complementary preclinical and clinical observations justify the safe use of L-BPA up to clinical phase III studies with L-BPA produced by the asymmetric pathway, originally presented by Malan and Morin in 1996.