Non-linear model for the kinetics of¹⁰B in blood after BPA–fructose complex infusion

Abstract

A numerical model with a memory effect was created to describe the kinetics of 10B in blood after a single 4-dihydroxyborylphenylalanine-fructose complex (BPA-F) infusion in boron neutron capture therapy (BNCT). The model formulation was based on the averaged data from 10 glioma patients from the Brookhaven National Laboratory (BNL) BNCT-trials. These patients received a 2 h i.v. infusion of a BPA-fructose complex that delivered 290 mg BPA/kg body weight. The model was validated by fitting the original BNL patient data and new patient data from the Finnish BNCT-trials. The new 3-parameter non-linear model provided mean absolute differences between the measured and estimated 10B concentrations in blood that were less than 3.9% when used to simulate actual patient irradiations that comprised two irradiation fields separated by a break to reposition the patient. The flexibility of the model was successfully tested with two different infusion protocols. The patient data were modelled with a two-compartment model and a bi-exponential fit for comparison. The 3-parameter model is better than previously described models in predicting the time course of blood 10B concentration after cessation of intravenous infusion of BPA-fructose.

Kohonen classification applying ‘missing variables’ criterion to evaluate the p‐boronophenylalanine human‐body‐concentration decreasing profile of boron neutron capture therapy patients

“…Until now, standard modeling techniques require, in advance, the knowledge of a mathematical analytical function, the parameters of which are determined on the basis of the best agreement between the experimental and estimated data [4,14,15]. Now, for this model we took advantage of the ANN property of not requiring that knowledge to adapt the relationship between the experimental and estimated data.…”

“…The prediction of the concentration profile of the BPA in blood after the last recorded measurement is highly necessary because the radiation dose depends on it. In the present work, the prediction of the concentration profile during the blind period extended up to 4 h is worked out by modeling it with a method based on the Kohonen neural network [2,3] employing the data (concentration profiles) of various lengths recovered from previous treatments reported in the literature [4][5][6][7][8][9]. The method is described and discussed.…”

“…Being the prediction of the decreasing side of the curve the most important aspect of the modeling in order to work out the radiation's dose of BNCT, we proceeded to recalculate algorithm (4) using the same concept applied for ANN. The error was calculated for each of the original experimental points of the curves located after passing 60 min of the peak's time, using the previous points to calculate the parameters of algorithm (4). The comparisons of the RMSPEs of both methods are shown in Table II.…”

1H MRS phantom studies of BNCT 10B‒carrier, BPA–F using STEAM and PRESS MRS sequences: Detection limit and quantification

“…The short TR can be either used to decrease the study duration or to increase the SNR by increasing the number of scans. However, it should be noted that low concentration of BPA in healthy brain tissue during BNCT (<2 mM, [8,10,11]) may limit the applicability of concentration ratio determination (see next section).…”

“…This information is essential when judging possibilities to study in vivo BPA concentration with 1 H MRS in such situations where BPA concentration is significantly decreased from the peak value, e.g., after neutron irradiation. It has been estimated that tumor and healthy tissue BPA concentrations during the BNCT irradiation are 5-6 and 1-2 mM, respectively [8,10,11]. Furthermore, quantification was performed for more dilute BPAsolutions (2.9 mM and 5.8 mM) compared to the previous study, where the studied BPA concentrations (7.2 mM and 11.5 mM) represented the estimated maximum BPA concentration in patient's brain during BNCT treatment (directly after the infusion of the BPA-F).…”