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Novel diagnostic and therapeutic radionuclides for the development

Novel diagnostic and therapeutic radionuclides for the development of innovative radiopharmaceuticals.

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Novel diagnostic and therapeutic radionuclides for the development

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  1. Novel diagnostic and therapeutic radionuclides for the development of innovative radiopharmaceuticals Holger Dorrer, Catherine Ghezzi, Ferid Haddad, Mikael Jensen, Ulli Köster, Cristina Müller, Bernd Pichler, Anna-Maria Rolle, Roger Schibli, Jonathan Siikanen, Andreas Türler, Stefan Wiehr, Konstantin Zhernosekov

  2. Radiometals for diagnostic imaging and therapy Objectives M☢ Receptor Chelator Peptide Abs Vitamins Photon or positron emitters 99mTc, 68Ga, … for imaging Particle emitters 90Y, 177Lu, … for radionuclide therapy applicable only with high specific activity and chemical purity

  3. Suitable Radionuclides • established • investigational High-energy proton induced reactions can produce most of the isotopes of the chart of nuclides.

  4. Do we need so many Radionuclides?

  5. Do we need so many Radionuclides? Radionucide Therapy delivery of therapeutic dose of ionizing radiation to the malignant cell Alpha,beta, electrons • cytotoxicity and therapeutic efficiency; • side-effects and limiting doses.

  6. New Terbium isotopes for therapy and diagnosis A Multi-Purpose Element 149Tb for targeted alpha therapy

  7. 50 mm Physics and Chemistry separation of isobar/pseudo-isobar ions Deposition of lanthanide ions ontozinc covered gold foil (15 mm x 8 mm) Foil holder for deposition of ion beam 9 Progress report Terbium-radioisotopes

  8. Tumor Kidney Preliminary Results ISOLDE 152Tb-PET the first in vivo application 24 h p.i ISOLDE Tumor Kidney 155Tb-SPECT the first in vivo application 19 h p.i

  9. Therapy: Alfa vs Beta ISOLDE 149Tb therapy with alpha Untreated Mice Alpha emitter 149Tb can be available from ISOLDE Day 16 after the Therapy Tumor Treated Mice investigation of the biological response to the different characteristics of the decay radiation in the same system Tumor PSI Tumor Kidney Beta emitter 161Tb available at PSI 161Tb therapy with beta the first therapy studies!Followed up by SPECT imaging

  10. 140Nd ε 3.37 d 140Pr β+ 2.4 3.4 m 140Ce Long-lived radionuclides for imaging 140Nd radiolabelled DOTA-mAb at day 12 post injection

  11. Towards Auger electron therapy M. Jensen et al., Hevesy Lab, DTU Risø, Denmark produce 71Ge with high specific activity at ILL micro-injection of 0.1 pl Na2GeO3 into the cell Incubate 1 hour Read out double strand breaks by gamma-H2AX assay Control cells injected with "cold" germanate solution ...work in progress: needs 131Cs, 140Nd, 165Er... from ISOLDE

  12. Spallation production of 149Tb 1.4 GeV ISOLDE PSB 1.0 GeV ISOLDE PSB 0.6 GeV ISOLDE SC

  13. Yields of 149Tb (As expected) the target and ionizer temperature have a crucial influence on the yields (valid for all surface-ionized lanthanides!), a high temperature of the tungsten ionizer is essential.

  14. Ways to optimize the 149Tb activity Action Gain factor Heat tungsten line more (2300–2400 °C)  5 Dy/Tb RILIS with setting optimized for A=149  2 ? Collect for 6 hours instead of 3 or 4 hours 1.3-1.6 Run with 2 A protons on target  2 Reduce delay until parcel leaves CERN 2 Estimated gain factors for 2012 with respect to collections performed in June 2011.

  15. Dedicated shielded transport containers • tungsten shielded POSISAFE from Lemer-Pax • certified as “Type A” for 90 MBq “unknown α activity”, i.e. 0.5 GBq 149Tb • “type B” certification for much higher activities under preparation • 10 reusable container available from PSI/Uni Bern/ILL

  16. Beam request : 25 shifts total in 2012 • Ta foil target + W surface ionizer, if possible with Dy/Tb RILIS : • 16 shifts in two beam times (8 shifts each) for 149Tb/152Tb/155Tb: • 5 nights (12 hours each) for collections to be shipped to PSI: • 20:00 – 02:00 collection of 152Tb • 02:00 – 08:00 collection of 149Tb • 09:00 shipment leaves to PSI • 5 x 12 hours = 60 hours = 8 shifts (incl. preparation) • 155Tb is collected in parallel on GHM (no extra shifts counted) • Ta foil target + W surface ionizer • 5 shifts to collect 134Ce, 140Nd and 165Tm/165Er • UCx, ThCx, LaCx or La target with surface ionizer • 1 shift to collect 131Cs • various targets/ion sources • 3 shifts to collect test samples of 47Sc, 71Ge, 71,72,74As, 73Se, 84Rb, 117mSn, 200,203Pb and 202-206Bi

  17. Thank you for your attention!

  18. Therapy planing

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