Additive effect of BPA and Gd-DTPA for application in accelerator-based neutron source F. Yoshida, K. Nakai, T. Yamamoto, A. Zaboronok, A. Matsumura Department of Neurosurgery, Faculty of Medicine, University of Tsukuba Background In neutron capture therapy, gadolinium compound effect results from gamma rays derived from the Gd (n, g) reaction. Gadolinium has a large neutron capture cross-section. However, due to the fast decrease in therapeutic concentration, it has not been used in neutron capture therapy. One of the features of the accelerator-based neutron source is short irradiation time, which is advantageous for gadolinium neutron capture therapy. If gadolinium is administered simultaneously with boron and is irradiated with neutrons, it might become a source of additional local gamma rays. Additive effect of BPA and Gd-DTPA in BNCT Experiment 1 Materials and Methods 1 Result 1 Experiment 2 Materials and Methods 2 (colony formation assay) C6 rat glioma cells (3 × 10 6 ) were inoculated in Wistar rats subcutaneously in 6 locations at the back (n = 5). BPA and Gd-DTPA were administrated via the tail vein as follows. ① BPA alone, ② Gd alone, ③ Gd and BPA simultaneously. Gd-DTPA concentration applied as clinically used (10ml/kg). BPA was administrated in the dose of 750  g/rat (150 g). The subcutaneous tumor was removed 15, 30, 60, 90, and 120 min after the drug administration. Boron and gadolinium concentration in tumors were measured by ICP- AES (ICPS-8100, Shimadzu, Tokyo, Japan). Cell lines: C6, V79, CT26 were used. Combined use of BPA (0, 10, 20, 40 ppm) and Gd-DTPA(0, 0.5, 5, 10 or 50ppm) with 1 × 10 4 cells. Neutron irradiation was performed at the Kyoto University Research Reactor (KUR) with the exposure time of 90 min. Result 2 Discussion & Conclusion Results University of Tsukuba The concentration of boron and gadolinium in the tumor was measured with time course. Fig. 2 Time course of a: Boron and b: Gadolinium concentration in rat subcutaneous tumors. : BPA/Gd-DTPA alone, : simultaneous administration of BPA and Gd-DTPA. The data were analyzed with the paired t-test. There was no significant difference between the sole administration and simultaneous administration. Linear Accelerator Wall Neutron generatorTreatment table Neutron beam Patient Fig. 1 Accelerator-based treatment apparatus not requiring nuclear reactor Fig. 3 Influence of Gd on BNCT in C6 (a), V79 (b) and CT26 (c) cell lines. Blue lines show the control (BPA only). Red lines show the result of the added 0.5 ppm of Gd. Green lines show the result of the added 5 ppm of Gd and purple lines show the result of the added 10 ppm of Gd (in CT26 cells 50 ppm of Gd was also used). In all cell lines the radiation-related damage increased with the increase of gadolinium concentration. (*p < 0.05, **p < 0.01, compared with Gd 0) a. b.c. 1.There was no significant difference in boron and gadolinium concentration in the subcutaneous tumor with sole or simultaneous administration. 2.Gadolinium concentration was about 8 ppm 30 minutes after the administration, and 4 ppm after 1 hour. 3.Additive effect of BPA and Gd-DTPA increased with the increase of the compound concentration. 4.The effect of Gd on radiosensitivity was more obvious in C6 and CT26 tumor cell lines rather than fibroblast-like V79 cell line. 1.In order to enhance the effect of BNCT, additional X-ray irradiation is often performed. 2.Gd-DTPA is widely clinically used as a contrast medium for MRI. 3.In the current study, we suggested that using BPA together with Gd-DTPA might enhance the effect of BNCT. 4.Although the metabolism of gadolinium is fast, its additional effect is seen with the increase of its concentration from 5 to 10 ppm. 5.Therefore, in BNCT using the accelerator-based neutron source with short irradiation time the additional curative effect from gadolinium might be expected. ** *