1. 1 1)C 6 Glial Tumor model on BALB-c-nu/nu (8W, ♂, 25g). Final Concentration of 2x10E5 cells/mouse. 2)0.5 mM-Compound-B [from Nesmeyanoy Institute of Organoelement Compounds] Local-injection 48hr before Neutron Beam Irradiation, Group-3 ([ 10 B]=55.4 ppm/C 6 Tumor Tissue) for 120 min (Totally 17.7Gy). Thermal neutron shield using Enriched Lithium-6 Fluoride Gold leaf was radiated by Neutron TLD (Thermo- luminescence dosimeter) against Γ-ray BNCT irradiation Stage for Clinical and Animal Studies Clinical Stage Animal Stage (Rail)

2. 2 Russian patent № 2402554, priority: July 17, 2008 Registered in State Registry of Patents on October 27, 2010 Japan patent No.2012-098918, priority: April 24, 2012 in Japan Carborane Cages from KATCHEM Ltd, Co., Czech Rep. 2013.02 Synthesis 2013.08 Experiments 2013.09

3. 3 Excitation peak at 655nm Emission peak at 665nm Emission peak Excitation peak 375 nm 657nm

4. 4 [A] Excitation Wavelength = 377.6 nm ( ～ 150mW) [B] Irradiation Wavelength = 657 nm ( ～ 578 mW) [C] Pulsed Frequency = 0.001 (6) ～ 1 kHz (657 nm) [C] [B] [A] [B] [C] [A]

5. 5 Spin Trapping Agents DMPO-(OH), -(Carbon) Radicals TMPD-NO ( 1 O 2 *) LD Laser 377.6 nm 635 nm ○ 657 nm 1: 2: 2: 1 DMPO (5, 5’-dimethyl-1-pyroline-N-oxide)-OH 1 1 : 1 TMPD (2,2,6,6-tetramethyl-4-pyperidone hydrochloride)-NO

6. 6 Prof. S. Okazaki an his original instrument Excitation light source (ELS), Emission spectrum (ES) and Lifetime (L) measurement installations ELS ES L

7. 7 Ultra-weak Emission Spectra of Singlet Oxygen sensitized by 10  M-Compound-B excited at 654 nm in MeOD and Saline The Decay Curves (DSO) of Singlet Oxygen sensitized by 10  M- Compound-B excited at 654 nm In MeOD and Saline  MD =1.00/Saline  =0.23/Saline  =?/MeOD MeOD

8. 8 N=10-18 SD=+/-(5-8)% Tumors 1: 5-ALA/PDT 2: BPA/BNCT 3: BNCT-  PDT 4: PDT-  BNCT Reduction Rate (%) at three weeks later 2 3 4 1

9. 9 I P-injection

10. Gyrotron Warming (33C) for 10min at 229GHz Duration Times (<36 hr)

11. 11

12. 12

13. 13 Comparing Anti-tumor Effects of IP or Local Administration of Compound-B

14. 14

15. 15

16. 16

17. ConditionsSlope e[slope x X]R2R2 Control0.404 (100.0%)0.988 Control (+Compound-B)0.286 (70.7%)0.996 PDT (+Light)0.349 (86.3%)0.975 PDT (+Compound-B +Light)0.196 (48.5%)0.690 Proton0.293 (72.5%)0.974 Proton (+Compound-B)0.136 (33.6%)0.973 Combination (Proton+Light)0.235 (58.1%)0.926 Comvination (+Compound-B +Light+Proton) 0.131 (32.4%)0.953 17

18. 18

19. 19 Scab C6 tumor entity Bleed- ing in tumor Fluore scence image before treat ments Scab form ation 24 hr after treat ments