Translational Evaluation of a Dodecaborated Albumin Conjugate With Maleimide as a Boron Delivery System for a Neutron Capture Reaction to an F98 Rat Glioma Model

Boron neutron capture therapy (BNCT) is a biologically targeted, cell-selective particle irradiation therapy that utilizes the nuclear capture reaction of boron and neutron. Recently, accelerator neutron generators have been used in clinical settings, and expectations for developing new boron compounds are growing. In this study, we focused on serum albumin, a well-known drug delivery system, and developed maleimide-functionalized closo-dodecaborate albumin conjugate (MID-AC) as a boron carrying system for BNCT. Our biodistribution experiment involved F98 glioma-bearing rat brain tumor models systemically administered with MID-AC and demonstrated accumulation and long retention of boron. Our BNCT study with MID-AC observed statistically significant prolongation of the survival rate compared to the control groups, with results comparable to BNCT study with boronophenylalanine (BPA) which is the standard use of in clinical settings. Each median survival time was as follows: untreated control group; 24.5 days, neutron-irradiated control group; 24.5 days, neutron irradiation following 2.5 hours after termination of intravenous administration (i.v.) of BPA; 31.5 days, and neutron irradiation following 2.5 or 24 hours after termination of i.v. of MID-AC; 33.5 or 33.0 days, respectively. The biological effectiveness factor of MID-AC for F98 rat glioma was estimated based on these survival times and found to be higher to 12. This tendency was confirmed in BNCT 24 hours after MID-AC administration. MID-AC induces an efficient boron neutron capture reaction because the albumin contained in MID-AC is retained in the tumor and has a considerable potential to become an effective delivery system for BNCT in treating high-grade gliomas.

Epoxyanthracene derivatives and dicarbonylation on benzene ring via HDDA-derived benzyne with oxazole

Here we report a capture reaction of hexadehydro–Diels–Alder derived benzyne with various substituted oxazoles. With methyl, hydrogen or phenyl as the substituent at 2-position of oxazole, we obtained epoxyanthracene derivative and dicarbonylation on benzene ring. The reaction does not require any catalyst and additive. The mechanism behind the reaction was investigated. The obtained polycyclic product structure has potential application value in optoelectronic materials. The availability of dicarbonylated arene implies the uniqueness of HDDA benzyne reaction compared with traditional benzyne.

Improvement of Conversion Ratio of Thorium Fuel in LWR by Adding Neutron Absorber

The reproduction factor of Th232 is high in the thermal energy range and there is a possibility to achieve the breeding in LWRs. However, it is necessary to improve the conversion ratio since the breeding is difficult in LWRs. The conversion ratio can be improved by suppressing capture rate of Pa233 and by promoting capture rate of Th232. In addition, these capture rates can be modified by adding neutron absorber. Therefore, the neutron absorber is focused for improving the conversion ratio in this study. The high resonance peaks of Pa233 capture cross section exist around 1∼100 eV. The resonance peaks of Th232 are higher than 10 eV. Thus, when the 1∼10 eV neutrons are suppressed in the fuel, the Pa233 resonance capture reaction is suppressed and the Th232 resonance capture reaction is promoted by neutron spectrum hardening. Therefore, six neutron absorbers that have high capture cross section peaks at 1∼10 eV were selected. The PWR pin cell calculations were carried out by Monte Carlo code MVP. The fuels are composed of a base material and an absorber. The base material is an oxidized fuel composed of U233(10 wt%), Th232(89.95 wt%), and Pa233(0.05 wt%). The amount of neutron absorber was adjusted so that the infinite multiplication factor becomes 1.33. The impact of adding neutron absorber on the reaction rate was evaluated. As the result, the hardening of the neutron spectrum leads increase of the capture rate of Pa233, and the capture rate of Th232 in the epithermal energy range is increased. The change of capture rate of Th232 is greater than that of Pa232. Therefore, the conversion ratio is found to be improved by adding neutron absorber.