In vivo boron-10 analysis for the pre-screening of compounds for BNCS

Abstract

An in vivo boron-10 screening technique was developed to analyze the boron biodistribution in a rabbit knee for the pre-screening of compounds for Boron Neutron Capture Synovectomy (BNCS). Three approaches were investigated: emission computed tomography (ECT), transmission computed tomography (TCT) and in vivo prompt gamma neutron activation analysis (IVPGNAA). Each was first studied using simulation-generated projection data. Experimental data collection systems were then constructed for TCT and IVPGNAA, and phantom experiments were conducted at the MIT Research Reactor (MITR) to verify simulation results. While TCT was predicted to have superior performance in terms of spatial resolution, temporal resolution and boron quantification, IVPGNAA was chosen for further development given the readily available neutron sources at the MITR. Assuming an 8.5x105 cm-2s-1 incident neutron flux, a 3.5mmx20mm beam, and a knee injection of 1.05mg 10B, one projection data set can be collected within 12 minutes, for reconstruction of relative 10B distribution in eight 40mm2 regions. The estimated uncertainty associated with reconstructed results, assuming a regional 2000 ppm concentration, is [approx.] 25%. Phantom experiments demonstrated the overall feasibility of IVPGNAA as a means of conveniently evaluating spatial and temporal characteristics of 10B in a rabbit knee.

(cont.) Animal experiments were then conducted at the MITR using 3.5kg anesthetized arthritic rabbits. Three boronated compounds were investigated, each with widely different in vivo spatial and temporal characteristics, as determined previously via dissection studies. Good agreement in egression behavior between IVPGNAA predictions and dissection study results was found for 2 compounds. The third compound was not detectable under experimental conditions, suggesting the possibility that the compound was not taken up by the synovium. This finding was consistent with the dissection study results. IVPGNAA is an invaluable tool for early rejection of compounds with poor characteristics, and can provide guidance for dissection studies of promising compounds.