Noninvasive quantitative in vivo mapping and metabolism of boronophenylalanine (BPA) by nuclear magnetic resonance (NMR) spectroscopy and imaging.
10B-enriched L-p-boronophenylalanine (BPA) is one of the compounds used in boron neutron capture therapy (BNCT). In this study, several variations of nuclear magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) were applied to investigate the uptake, clearance and metabolism of the BPA-fructose complex (BPA-F) in normal mouse kidneys, rat oligodendroglioma xenografts, and rat blood. Localized 1H MRS was capable of following the uptake and clearance of BPA-F in mouse kidneys with temporal resolution of a few minutes, while 1H MRSI was used to image the BPA distribution in the kidney with a spatial resolution of 9 mm3. The results also revealed significant dissociation of the BPA-F complex to free BPA. This finding was corroborated by 1H and 11B NMR spectroscopy of rat blood samples as well as of tumor samples excised from mice after i.v. injection of BPA-F. This investigation demonstrates the feasibility of using 1H MRS and MRSI to follow the distribution of BPA in vivo, using NMR techniques specifically designed to optimize BPA detection. The implementation of such procedures could significantly improve the clinical efficacy of BNCT.
Bendel
Peter
P
Chemical Research Support, The Weizmann Institute of Science, Rehovot 76100, Israel. Peter.Bendel@weizmann.ac.il
Margalit
Raanan
R
Koudinova
Natalia
N
Salomon
Yoram
Y
D000818:Animals; D001896:Boron Compounds / Q000378:metabolism*; D016754:Boron Neutron Capture Therapy; D007668:Kidney / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats
C436045:4-dihydroxyborylphenylalanine; D001896:Boron Compounds; D010649:Phenylalanine