Uptake and washout of borocaptate sodium and borono-phenylalanine in cultured melanoma cells: a multi-nuclear NMR study.
The cellular uptake and washout of the two principal boron neutron capture therapy (BNCT) agents, borocaptate sodium (BSH) and borono-phenylalanine (BPA), were monitored on-line, noninvasively, using nuclear magnetic resonance (NMR) spectroscopy. The uptake and washout of inorganic borate (B(i)) was also followed for comparison. M2R mouse melanoma cells grown on polystyrene microspheres were perfused inside the NMR sample tube. (11)B NMR was used to detect the presence of B(i), BSH and BPA, and (19)F NMR was applied to detect fluorinated BPA ((19)F-BPA). The results revealed chemical modifications of BSH due to spontaneous formation of the borocaptate dimer, BSSB, in the culture medium. BPA readily formed a complex with glucose contained in the culture medium but was also converted in the cells to a yet unidentified compound in a reaction that probably involves the hydrolysis of BPA and the release of B(i). The cellular accumulation ratio for BPA was significantly higher than 1 and was also significantly higher than that for BSH. On the other hand, the cellular retention time observed for BSH was much longer than for BPA, indicating a strong trapping of BSH in cells.
Panov
V
V
Department of Chemical Services, The Weizmann Institute of Science, Rehovot, Israel.
Salomon
Y
Y
Kabalka
G W
GW
Bendel
P
P
D000818:Animals; D001692:Biological Transport; D001894:Borohydrides / Q000737:chemistry / Q000378:metabolism*; D001896:Boron Compounds / Q000737:chemistry / Q000378:metabolism*; D003470:Culture Media; D008545:Melanoma; D051379:Mice; D019906:Nuclear Magnetic Resonance, Biomolecular; D010477:Perfusion; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D001894:Borohydrides; D001896:Boron Compounds; D003470:Culture Media; D011838:Radiation-Sensitizing Agents; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D010649:Phenylalanine; C033685:4-boronophenylalanine