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Proton nuclear magnetic resonance measurement of p ‐boronophenylalanine (BPA): A therapeutic agent for boron neutron capture therapy
Author(s) -
Zuo C. S.,
Prasad P. V.,
Busse Paul,
Tang L.,
Zamenhof R. G.
Publication year - 1999
Publication title -
medical physics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 180
eISSN - 2473-4209
pISSN - 0094-2405
DOI - 10.1118/1.598617
Subject(s) - neutron capture , in vivo , chemistry , nuclear magnetic resonance , nuclear magnetic resonance spectroscopy , proton nmr , proton therapy , boron , radiochemistry , proton , neutron , materials science , physics , nuclear physics , microbiology and biotechnology , organic chemistry , biology
Noninvasive in vivo quantitation of boron is necessary for obtaining pharmacokinetic data on candidate boronated delivery agents developed for boron neutron capture therapy (BNCT). Such data, in turn, would facilitate the optimization of the temporal sequence of boronated drug infusion and neutron irradiation. Current approaches to obtaining such pharmacokinetic data include: positron emission tomography employing F‐18 labeled boronated delivery agents (e.g., p ‐boronophenylalanine), ex vivo neutron activation analysis of blood (and very occasionally tissue) samples, and nuclear magnetic resonance (NMR) techniques. In general, NMR approaches have been hindered by very poor signal to noise achieved due to the large quadrupole moments of B‐10 and B‐11 and (in the case of B‐10) very low gyromagnetic ratio, combined with low physiological concentrations of these isotopes under clinical conditions. This preliminary study examines the feasibility of proton NMR spectroscopy for such applications. We have utilized proton NMR spectroscopy to investigate the detectability of p ‐boronophenylalanine fructose (BPA‐f) at typical physiological concentrations encountered in BNCT. BPA‐f is one of the two boron delivery agents currently undergoing clinical phase‐I/II trials in the U.S., Japan, and Europe. This study includes high‐resolution1 H spectroscopic characterization of BPA‐f to identify useful spectral features for purposes of detection and quantification. The study examines potential interferences, demonstrates a linear NMR signal response with concentration, and presents BPA NMR spectra in ex vivo blood samples and in vivo brain tissues.