Proton nuclear magnetic resonance measurement of p-boronophenylalanine (BPA): A therapeutic agent for boron neutron capture therapy

Noninvasive in vivo quantitation of boron is necessary for obtaining pharma cokinetic data on candidate boronated delivery agents developed for boron n eutron capture therapy (BNCT). Such data, in turn, would facilitate the opt imization of the temporal sequence of boronated drug infusion and neuron ir radiation. Current approaches to obtaining such pharmacokinetic data includ e: positron emission tomography employing F-18 labeled boronated delivery a gents (e.g. p-boronophenylalanine), ex vivo neutron activation analysis of blood land very occasionally tissue) samples, and nuclear magnetic resonanc e (NMR) techniques. In general, NMR approaches have been hindered by very p oor signal to noise achieved due to the large quadrupole moments of B-10 an d B-11 and tin the case of B-10) very low gyromagnetic ratio, combined with low physiological concentrations of these isotopes under clinical conditio ns. This preliminary study examines the feasibility of proton NMR spectrosc opy for such applications. We have utilized proton NMR spectroscopy to inve stigate the detectability of p-boronophenylalanine fructose (BPA-f) at typi cal physiological concentrations encountered in BNCT. BPA-f is one of the t wo boron delivery agents currently undergoing clinical phase-I/II trials in the U.S., Japan, and Europe. This study includes high-resolution H-1 spect roscopic characterization of BPA-f to identify useful spectral features for purposes of detection and quantification. The study examines potential int erferences, demonstrates a linear NMR signal response with concentration, a nd presents BPA NMR spectra in ex vivo blood samples and in vivo brain tiss ues. (C) 1999 American Association of Physicists in Medicine. [S0094-2405(9 9)00407-1].