Derivations of relative biological effectiveness for the high-let radiations produced during boron neutron capture irradiations of the 9l rat gliosarcoma in vitro and in vivo

Purpose: Relative biological effectiveness (RBE) values for the high linear-energy-transfer particles produced during boron neutron capture therapy have generally been based on theoretical considerations or on in vitro experiments. The purpose of this study was to independently determine RBE values for all of the boron neutron capture therapy dose components. Methods and Materials: Clonogenic cell survival data were obtained for 9L rat gliosarcoma cells irradiated in the Brookhaven Medical Research Reactor thermal neutron beam both in vitro and as an intracerebral tumor. These data were analyzed using the linear quadratic model for cell survival to derive measured RBE values for all beam components and for a number of different boron compounds. Results: In the absence of boron, the combined effects of the protons from the nitrogen capture, 14N(n,p) 14C, and the fast neutron scatter, 1H(n,n′)p, reactions generated RBEs of 3.7 in vitro and 3.2 in an in vivo/in vitro excision assay, compared to 250 kVp X rays using an end point of 1% cell survival. Apparent RBEs for the 10B(n,α) 7Li reaction products were calculated from cell survival data following reactor irradiations in the presence of the amino acid p-boronophenylalanine, the sulfhydryl dodecaborate monomer or dimer, or boric acid. Apparent RBEs for the 10B(n,α) 7Li reaction ranged from 1.2 to 9.8 depending on which boron compound was used. RBEs from the in vitro studies were consistently higher than from the in vivo/in vitro studies. Under any conditions, the apparent RBE for the 10B(n,α) 7Li reaction with p-boronophenylalanine was higher than that with any other boron compound tested. Conclusions: Generally accepted RBE values for the fast neutron and 14N(n,p) 14C reaction components of the total dose are too low. The apparent RBEs calculated for the 10B(n,α) 7Li reaction were compound-dependent and consistent with differences in the distribution of 10B relative to glioma cell nuclei.