title: In vitro studies on stability of L-p-boronophenylalanine-fructose complex (BPA-F).
abstract: Boron neutron capture therapy (BNCT) is an experimental drug-targeted treatment combining tumour-seeking boronated drug(s) and subsequent ¹⁰B activation by neutrons. Synthetic amino acid, L-p-boronophenylalanine (BPA), administered as a fructose complex (BPA-F) is used in BNCT trials. We tested the in vitro biological and structural stability of the BPA-F as a function of time (11 days). The BPA-F samples were analyzed using biological bacterial endotoxin and sterility tests. Visual tests were clarity, degree of opalescence and coloration according to European Pharmacopoeia. The structural stability of the BPA-F was monitored via ¹H NMR signal intensity of the aromatic protons of the BPA-F samples. A slight change of BPA-F samples in coloration was observed during storage. BPA-fructose complex remained sterile and bacterial endotoxin tests were negative. In the end of study period, relative intensity of the (1)H NMR signals of the BPA-F sample was ≥ 90% of the initial relative intensity. The biological properties of the BPA-fructose complex and chemical structure of the complex remained the same during the test period. Visually the solutions stayed clear, but there was a slight change in colour. The tests indicate that the prepared batch of BPA-F complex can be used for the patient infusion at least for a week.
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, Helsinki University Central Hospital, Finland. sami.heikkinen@helsinki.fi
authors.forename: Sami
authors.initials: S
authors.lastname: Heikkinen
authors.forename: Sauli
authors.initials: S
authors.lastname: Savolainen
authors.forename: Petri
authors.initials: P
authors.lastname: Melkko
mesh_terms: D016754:Boron Neutron Capture Therapy; D005632:Fructose / Q000737:chemistry* / Q000528:radiation effects*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000528:radiation effects; D011829:Radiation Dosage
chemical_list: C535012:(benzoylphenyl)alanyl; D005632:Fructose; D010649:Phenylalanine