L-Boronphenylalanine Biodistribution Dynamics in the Organs of Mice with Subcutaneous Tumor Xenograft is a Model to Assess Neuron Sources Efficiency in Boron Neutron Capture Therapy.

Abstract

Boron neutron capture therapy (BNCT), due to its high biological efficiency, is one of the most promising methods of radiation therapy for malignant tumors. Currently, research in this area has received momentum due to the emergence of fundamentally new compact neutron sources suitable for clinical use. The aim of the investigation was to study L-boronphenylalanine (L-BPA) biodistribution in the organs of experimental animals with subcutaneous tumor xenografts, and evaluate the application of the experimental model to assess the effectiveness of new neutron sources.

Materials and methods: The experiments were carried out on BALB/c mice with subcutaneous xenograft of mouse adenocarcinoma CT26. L-boronphenylalanine in a molar excess of fructose was administered intravenously at a dose of 350 mg/kg, the organs under study were taken 1.5, 3, 6, and 24 h after drug administration. The content of the ¹⁰B isotope was analyzed using inductively coupled plasma mass spectroscopy (ICP-MS). The absence of toxic effects was verified pathomorphologically.

Results: The maximum L-BPA content in the tumor was 142.0±4.41 μg/g 1.5 h after drug administration. The minimum therapeutic concentration of L-BPA in the tumor persists up to 5.4 h after drug administration. Among normal organs, the maximum content was observed in the kidneys, it is most likely being associated with the structural and functional features of the organ rather than the true content of L-BPA in the tissues. Histological studies revealed no structural disorders and dystrophic changes in tissues against the background of L-BPA introduction.

Conclusion: The results of the study demonstrate the feasibility of the studied tumor model to evaluate the efficiency of new neutron sources for BNCT. The L-borophenylalanine content in the tumor and the time of maintaining the minimum therapeutic concentration appeared to be sufficient for effective BNCT. The high contrast of ¹⁰B accumulation relative to non-pathological tissues minimizes the possible side effects of BNCT.