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Use of RIB facilities for producing isotopes for cancer treatment by DART

Use of RIB facilities for producing isotopes for cancer treatment by DART. Itzhak Kelson Tel Aviv University & Althera Medical Ltd. DART in a nutshell.

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Use of RIB facilities for producing isotopes for cancer treatment by DART

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  1. Use of RIB facilities for producing isotopes for cancer treatment by DART Itzhak Kelson Tel Aviv University & Althera Medical Ltd

  2. DART in a nutshell • DART (Diffusing Alpha-emitters Radiation Therapy): a new concept in radiation therapy which may enable therapeutic tumor doses with negligible damage to nearby healthy tissue • Comprises three elements: • The use of alpha particles rather than photons or electrons • Enhancement of the therapeutic range of alpha particles from microns to millimeters • Utilization of the different properties of malignant and healthy tissues to ensure minimal collateral damage

  3. Alpha particle essentials • Emitted by readily available isotopes • Densely ionizing (LET ≈ 100 keV/ µm) • Range in tissue: 40 – 90 µm • Possess all benefits of high-LET radiation: • Direct ionization of the DNA  complex DNA lesions • Biological effect insensitive to hypoxia, dose rate, cell cycle • Single hit to the nucleus may induce cell death • Short range may guarantee sparing adjacent tissue … but also limits the use against solid tumors

  4. The idea • Rather than a source that emits alpha particles - a source that emits alpha-emitting atoms • The source is impregnated with small activities of 224Ra • When 224Ra decays its daughter atoms recoil out of the source (Emax~100 keV) • The atoms disperse near the source, forming a cluster of alpha emissions extending over several millimeters

  5. Generator α Implanted Source 212Bi 224Ra decay chain 228Th α 1.91 y α α 220Rn 224Ra 216Po 212Pb 0.15 s 55.6 s 3.66 d β 10.64 h Diffusing Atoms α 208Tl 60.6 m β β 60.6 m 3.05 m α 212Po 208Pb 0.3 µs stable

  6. - V 228Th panel + V Source preparationelectrostatic collection of 224Ra Needle (source) Field lines

  7. A B C D E F All: 212Pb autoradiography of murine squamous cell carcinoma (SQ2)

  8. Mouse treated with a placebo source Mouse treated with a 800 nCi source

  9. Source preparation (future plant) 228Th +V -V Typical dimensions: L=100 cm, R=3 cm Typical 228Th activity: 10 μCi/cm2 Each unit produces ~2000 treatments/year

  10. Design criteria for 228Th generators • 228Th activity ~10 μCi/cm2 • 224Ra desorption probability ~40% • No knock-out of 228Th atoms • Safe, low-cost production • Long operational lifetime

  11. α 228Ra 228Th 227Ac 228Fr 228Ac 226Ra 228Ac 228Th 227Ra 228Th 232U 1.9 y 42 m 1.9 y 1600 y 38 s 6.2 h 6.2 h 5.8 y 22 y 1.9 y 69 y β β β β β 228Th Production Schemes (n,γ) σ=13b (n,γ) σ=902b

  12. 228Fr scheme - quantitative aspects • Typical DART treatment ~100 μCi 224Ra (1.7×1012 atoms) • 228Th atoms per treatment ~1013 • Assuming 228Fr production rate of 1012 atoms/s: ~10 seconds per treatment ~200 seconds per cm2 of generator

  13. Design criteria for 228Th generators - RIB • 228Th activity ~10 μCi/cm2 • 224Ra desorption probability ~40% • No knock-out of 228Th atoms • Safe, low-cost production • Long operational lifetime

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