1. Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg Ytterbium-169 Based High Dose Rate Brachytherapy Alexander Bogdanov, Atommedcenter LLC 1

2.  High Dose Rate (HDR) therapy of both surface and internal cancers  Therapy of head-neck cancers  Near critical organ localization therapy  Endovascular radio- surgery and to prevent rest enosis in stent operations Why use Yb-169 based High Dose Rate micro sources 2 Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg A new approach to the cancer therapy, improving quality of therapy, minimizing radiation dose on healthy tissues and reducing risks of further complications

3. The Main Advantages of Yb-169 Micro-sources Radionuclide:Co-60Cs-137Ir-192Yb-169Tm-170I-125Pd-103 Average energy of photon emission 1250 keV662 keV380 keV93 keV84 keV28 keV21 keV Half-life5,3 years30,2 years74 days32 days128 days59,4 days17 days  Softer emission spectrum (63–217 keV) compared with Ir-192 and Co-60 sources  They can be used for treatment of superficial cancers and internal cancers  They can be used with any apparatus for brachytherapy  Easy to handle  This sources can be used for endovascular radiosurgery and prevent restenosis in stent operations  Equivalent activity from 0.5 to 15 Ci 3 Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg

4. Yb-169 Source Design This design allows using Yb-169 based HDR micro sources with any commercially available apparatuses for brachytherapy Tube capillary Bottom-globule Yb 2 O 3 powder The enrichment of Yb isotope ω( 168 Yb) = 35.8±0.3% Currently available techniques allows enrichment up to 90% Before an irradiation titanium capsule contains of Ytterbium oxide powder (Yb 2 O 3 ), enriched by stabile isotope Yb-168 Titanium capsule is housed in a steel capsule with a tail (cable and shaft) 4 Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg

5. Pre-clinical Trials of Yb-169 Based HDR Brachytherapy Positive biological effect of the source has been proved on tumors in animals Irradiation of rats with sarcoma М-1 by Yb-169 based HDR micro sources 20 days after irradiation with Yb-169 Dynamics of tumor volume change after irradiation with Yb-169 no irradiation 5 Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg

6. Current Status of the Project 6 Currently the project is under transition to the clinical trials On the previous project phases the following tasks has been completed:  Calculations and durability tests of the Yb-169 sources;  Reactor irradiation study of the construction materials used for manufacturing source body;  Experimental estimation of the absorbed doses in the tissue equivalent phantom;  Experimental study of the dose characteristics using water phantom;  Study of the medical and biological characteristics of the Yb-169 sources;  Recommendations on the medical use and radiation safety of the Yb-169 sources. Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg

7. 7 Market Potential Estimation The market size (Russia) is estimated at 500 HDR apparatuses (~3000 src/year) Average cost of therapy is “1” Initial high investment in the building up radiation therapy complex will be later compensated by lower operational expenses compared to other therapy methods! Potential consumers:  FSBI “N.N.Blokhin RCRC” RAMS”  P.A. Herzen Moscow Cancer Research Institute  Federal State Healthcare Institution Clinical Hospital No. 8 of FMBA of Russia, Obninsk, Kaluga Oblast  Russian Scientific Center of Roentgenoradiology  Federal State Healthcare Institution L.G. Sokolov Clinical Hospital No. 122 of FMBA of Russia, St. Petersburg  Medical Radialogical Research Center, Obninsk  State Medical and Preventive Institution Chelyabinsk District Clinical Oncological Dispensary, Chelyabinsk Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg

8. 8 Market. Main Players The major players of the automated brachytherapy complexes market are the following:  Average price of the imported brachytherapy complexes in Russia is 30-35 mil. rub., while Russian- made complexes cost around 18 – 25 mil. rub  Со-60 and Ir-192 are mainly used as radiation sources for brachytherapy Yb-169 until now is not used in clinical practice for brachytherapy CompaniesCountryProduction for brachytherapy Varian Medical SystemsUSA GammaMedplus, GammaMedplus3/24, Varisource, GammaMed 12 Eckert & Ziegler BEBIG GmbHGermany MultiSource-HDR, Bebig Curietron LDR/MDR, Сurietron 192 Oris Nucletron (bought by Elekta in Sept. 2011) Sweden Selectron LDR, microSelectron LDR/MDR, microSelectron-HDR, microSelectron-PDR, Seed- Selectron, Selectron-HDR BuchlerGermanyGMBH JSC «NIITFA"RussiaAGAT-VT Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg

9. 9 Cooperation. Partners Cyclotron Co., Ltd, Obninsk, Manufacturing a titanium capsule containing Yb-168 oxide Medical Radialogical Research Center Study of the dosimetric, biological and medical characteristics of Yb-169 sources “Isotope Technologies”, Minsk Source manufacture Technical tests JSC IRM, г. Yekaterinburg Titanium capsule irradiation inside a reactor Coordination Commercialization Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg

10. 10 Proposal for cooperation with Varian  Ytterbium-169 ( 169 Yb) based HDR micro-sources for HDR  Results of pre-clinical trials  Afterloader for HDR w/out 60 Co/ 192 Ir-conteiner, applicators and accessories (or Mick Radio-Nuclear Instruments)  3D treatment planning system Brachytherapy of breast, prostate cancer; head-neck localizations and other surface and internal cancers Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg Clinical trials USA Russia

11. 11 Contacts: Alexander Bogdanov aabogdanov@atommedcenter.ru Tel.: +7 495 232 0345 Moscow, Russia, 115230 Warshavskoye sh, 46 Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg

12. 12 Приложения Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg

13. 13 Models and dimensions of Yb-169 based high-energy micro sources Source model Overall dimensions, mm Power air cerma on distance 1m, mGy/h Equivalent activity, Bq (Ci) External Sources with Holder (Plug and Shaft) Active core D1D1 L1L1 DL*L*d*d*l*l* GYb169М04.210 GYb169М04.410 GYb169М04.111 GYb169М04.211 GYb169М04.311 GYb169М04.411 GYb169М04.610 1,1±0,055,0+0,11,1±0,051000-30000,72,1 0,77 1,55 4,64 7,73 11,59 15,45 23,18 1,9х10 10 (0,5) 3,7х10 10 (1) 1,1х10 11 (3) 1,8х10 11 (5) 2,8х10 11 (7.5) 3,7х10 11 (10) 5,6х10 11 (15) GYb169М05.210 GYb169М05.410 GYb169М05.111 GYb169М05.211 GYb169М05.311 GYb169М05.411 GYb169М05.610 1,1±0,055,0+0,11,1±0,051000-30000,72,1 0,77 1,55 4,64 7,73 11,59 15,45 23,18 1,9х10 10 (0,5) 3,7х10 10 (1) 1,1х10 11 (3) 1,8х10 11 (5) 2,8х10 11 (7.5) 3,7х10 11 (10) 5,6х10 11 (15) GYb169М06.210 GYb169М06.410 GYb169М06.111 GYb169М06.211 GYb169М06.311 GYb169М06.411 GYb169М06.610 1,1±0,055,0+0,11,1±0,051000-30000,72,1 0,77 1,55 4,64 7,73 11,59 15,45 23,18 1,9х10 10 (0,5) 3,7х10 10 (1) 1,1х10 11 (3) 1,8х10 11 (5) 2,8х10 11 (7.5) 3,7х10 11 (10) 5,6х10 11 (15) Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg

14. 14 Energy spectrum (or distribution) of gamma quanta Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg

15. 15 Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg The measurement of absorbed dose distribution in a mammary gland phantom using a tissue equivalent phantom gland phantom using a tissue equivalent phantom

16. 16 Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg Three models of a steel construction depending on a holder design 1. Titanium capsule 2. Cable 3. 169 Yb 4. Steel capsule 5. Plug 6. Shaft * Sizes for inquiries (are defined by the customer) GYT169M04 GYT169M05 GYT169M06

17. Relative Distribution of Yb-169 Dose in Living Tissues “Organ” of human phantom Absorbed dose rate, Gy/min ovaries0,00011±0,000013 bowel0,00019±0,0009 lung (left)0,009±0,0013 stomach / ventriclus0,00078±0,00010 liver0,0016±0,00020 thyroid gland0,0009±0,0001 rectum0,0005±0,0001 bone marrow0,0061±0,0033 esophagus0,012±0,010 bladder0,00005±0,0002 brain0,00039±0,0002 salivary glands0,0037±0,0023 17 Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg

18. 18 Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg Dependence of relative tumor volume change ST on the time after irradiation

19. Photos of Yb-169 based HDR micro sources Operational wound at a cancer of a mammary gland with the subsequent Brachytherapy by radioisotope High energy micro source on basis of 169 Yb Steel capsuleShaft 19 Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg

20. 20 Statistics of cancer Структура злокачественных новообразований мужского населения России Структура злокачественных новообразований женского населения России Research and Practical Conference “Accelerators and Radiation technologies for the Futures of Russia” 28-29 September 2012, Saint-Petersburg