Proton magnetic resonance spectroscopy of a boron neutron capture therapy 10B-carrier, L-p-boronophenylalanine-fructose complex

Boron neutron capture therapy (BNCT) is a radiotherapy that has mainly been used to treat malignant brain tumours, melanomas, and head and neck cancer. In BNCT, the patient receives an intravenous infusion of a B carrier, which accumulates in the tumour area. The tumour is irradiated with epithermal or thermal neutrons, which result in a boron neutron capture reaction B(n,α)Li. This generates heavy particles that damage tumour cells. In Finland, boronophenylalanine fructose (BPA-F) is used as the B-carrier. The boron neutron capture reaction is responsible for the main therapeutic dose in BNCT, and therefore all information about boron accumulation in the tumour area is valuable. Currently, the drifting of boron from blood to tumour as well as the spatial and temporal accumulation of boron in the brain, are not precisely known. The BNCT treatment planning in Finland is based on estimations of boron concentrations in tumour and normal brain. These concentratins, in turn, are based on whole blood boron concentration, and assumption of constant boron concentration ratios for blood-to-tumour (1:3.5) and bloodto-normal brain (1:1). During the irradiation, the whole blood boron concentration is estimated with kinetic models from the whole blood boron concentrations of previously collected periodic blood samples, where boron concentration is determined with inductively coupled plasma-atomic emission spectrometry (ICP-AES). However, using these constant concentration ratios of blood-to-tumour or blood-to-normal brain produces significant uncertainties in estimating of the boron concentration in the normal brain and tumour. Therefore, new methods would be needed to determine the boron concentration in the brain non-invasively. Proton magnetic resonance spectroscopy (H MRS) could be used for selective BPA-F detection and quantification as aromatic protons of BPA resonate in the spectral region, which is clear of brain metabolite signals. This study, which included both phantom and in vivo studies, examined the validity of MRS as a tool for BPA detection. In the phantom study, BPA quantification was studied at 1.5 and 3.0 T with single voxel H MRS, and at 1.5 T with magnetic resonance imaging (MRSI). The J-modulation of a coupled spin system of BPA aromatic protons complicates the determination of transverse relaxation time as well as the intensity measurement of the BPA signal when uncoupled resonance is used as the concentration reference. Therefore, the response curve of aromatic protons to the PRESS sequence was calculated and the results were used for T2 determination and intensity corrections. The detection limit of BPA was determined in phantom conditions at 1.5 T and 3.0 T with two different voxel