Biodistribution of 10B in Glioma Orthotopic Xenograft Mouse Model after Injection of L-para-Boronophenylalanine and Sodium Borocaptate.

Natalya V. Gubanova,Alphiya R. Tsygankova,Alexander V. Romashchenko,Evgenii L. Zavjalov,Yuriy L. Orlov

doi:10.3390/biomedicines9070722

Abstract

Boron neutron capture therapy (BNCT) is based on the ability of the boron-10 (10B) isotope to capture epithermal neutrons, as a result of which the isotope becomes unstable and decays into kinetically active elements that destroy cells where the nuclear reaction has occurred. The boron-carrying compounds—L-para-boronophenylalanine (BPA) and sodium mercaptoundecahydro-closo-dodecaborate (BSH)—have low toxicity and, today, are the only representatives of such compounds approved for clinical trials. For the effectiveness and safety of BNCT, a low boron content in normal tissues and substantially higher content in tumor tissue are required. This study evaluated the boron concentration in intracranial grafts of human glioma U87MG cells and normal tissues of the brain and other organs of mice at 1, 2.5 and 5 h after administration of the boron-carrying compounds. A detailed statistical analysis of the boron biodistribution dynamics was performed to find a ‘window of opportunity’ for BNCT. The data demonstrate variations in boron accumulation in different tissues depending on the compound used, as well as significant inter-animal variation. The protocol of administration of BPA and BSH compounds used did not allow achieving the parameters necessary for the successful course of BNCT in a glioma orthotopic xenograft mouse model.

Highlights

IntroductionDespite considerable efforts to develop new drugs and treatments, patients’ mean overall survival has increased by only three months (from 12 to 15 months)
Therapy for malignant tumors in the human brain is rather challenging
The elaboration of targeted radiotherapy methods is a promising approach for brain tumor therapy [1]

Summary

Introduction

Despite considerable efforts to develop new drugs and treatments, patients’ mean overall survival has increased by only three months (from 12 to 15 months). Their invasive nature and location in vital regions of the human brain make these types of tumors difficult for surgery; adjuvant therapy does not provide the desired results. The elaboration of targeted radiotherapy methods is a promising approach for brain tumor therapy [1]. One such treatment option may be boron neutron capture therapy (BNCT).

Methods

Results

Conclusion