1. Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg Neutron Sources for Neutron Capture Therapy S.V. Golubev 1, V.A. Skalyga 1, V.G. Zorin 1, I.V. Izotov 1, S.V. Razin 1, A.V. Sidorov 1 A.V. Maslennikova 2 O. Tarvainen 3, H. Koivisto 3 1 Institute of Applied Physics RAS 2 Nizhny Novgorod State Medical Academy 3 Jyvaskylan Yliopisto University of Jyvaskyla

2. Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg Concepts of Neutron Capture Therapy (NCT) The mean free path of alpha particle is comparable with the cell size:The mean free path of alpha particle is comparable with the cell size: 4 He 2+ (9 µm) 4 He 2+ (9 µm) 7 Li 3+ (6 µm ) 7 Li 3+ (6 µm ) Ionization leads to the double- stranded break of DNA, which results in the cell’s deathIonization leads to the double- stranded break of DNA, which results in the cell’s death The mean free path of alpha particle is comparable with the cell size:The mean free path of alpha particle is comparable with the cell size: 4 He 2+ (9 µm) 4 He 2+ (9 µm) 7 Li 3+ (6 µm ) 7 Li 3+ (6 µm ) Ionization leads to the double- stranded break of DNA, which results in the cell’s deathIonization leads to the double- stranded break of DNA, which results in the cell’s death 10 B + n th  11 B*  7 Li (0.84 MeV)+  (1.47MeV) +  (0.48 MeV) (94 %) The 10 B(n,  ) 7 Li reaction has a very large cross section of 3837 barns for thermal neutrons 10 B + n th  11 B*  7 Li (0.84 MeV)+  (1.47MeV) +  (0.48 MeV) (94 %) The 10 B(n,  ) 7 Li reaction has a very large cross section of 3837 barns for thermal neutrons

3. Description of the solution and technology High biological efficiency Possibility of the treatment of neoplasms, which are resistant to all other forms of radiation, Glioblastoma multiforme, metastasis of melanoma Improving the efficiency of the standard methods of radiation therapy in combination with NCT High selectivity effect on the tumor Conditions for effective use Highest contrast content of 10 B in diseased and healthy tissue Available sources of neutrons with reasonable performance (neutron flux > 10 9 n/cm 2 s, neutron energy ~ 10 eV to ~ 10 (40) keV) Types of neutron sources: nuclear reactors, accelerators, neutron generators (D-D / D-T) More than 1000 operations have been made in the world using nuclear reactors

4. Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg Clinical Research Institute HUCH Ltd Sitra, Finnish Innovation Fund VTT Ventures Ltd Clinical Research Institute HUCH Ltd Sitra, Finnish Innovation Fund VTT Ventures Ltd

5. Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg Source D+ 50 – 150 mA (< 1 mA/cm 2 ) Source D+ 50 – 150 mA (< 1 mA/cm 2 ) Acceleration TiD 2 Target 1mA D +  10 8 n/s TiD 2 Target 1mA D +  10 8 n/s Moderator (D 2 O) and collimator Moderator (D 2 O) and collimator Neutron beam D + D  He 3 (0,82 MeV) + n (2,45 MeV) D + T  He 4 (3,5 MeV) + n (14,01 MeV) D + D  He 3 (0,82 MeV) + n (2,45 MeV) D + T  He 4 (3,5 MeV) + n (14,01 MeV) RF or ECR (2,45 GHz) 100–250 keV 10 7 – 10 8 n/s· cm 2

6. Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg f > 37 GHz, Р > 100 kV High frequency and high power of radiation: f > 37 GHz, Р > 100 kV Current density (> 500 mA/cm 2 ) Neutron flux ~ 10 10 n/s· cm 2 f > 37 GHz, Р > 100 kV High frequency and high power of radiation: f > 37 GHz, Р > 100 kV Current density (> 500 mA/cm 2 ) Neutron flux ~ 10 10 n/s· cm 2 High-current ECR ion source

7. Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg Market The key difference between the project’s product and the existing solutions on the market: Now NCT is performed using nuclear reactors, which essentially is a hundred times more expensive than the proposed solutions. The cost of a medical complex on the basis of the accelerator, according to Japanese experts, is between 20 and 40 million dollars, which is ten times more expensive. Segment of the market the project’s product is targeted on: - Medical equipment Potential users of the project: Medical oncology centers Demand for the product in the market. The official cost of treatment in Boneca clinic (Helsinki, Finland) is about 20000 euro, herewith the maintance of nuclear reactor is paid by the goverment. Cancers incidence (glial brain tumors, some cancers of central nervious system, oral cavity and pharynx, recurrent squamous cell carcinoma of the head and neck) according to official statistics is about tens of thousands of people a year, so market’s size is at 100 million euro per year.

8. Co-investors – manufacturers of gyrotrons «GYCOM Ltd» Institute of applied physics RAS Nizhny Novgorod State University Nizhny Novgorod State Medical Academy All-russian research institute of experimental physics JSC «Afrikantov OKBM» Volga Regional Medical Center Project team and cooperation