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Klinik und Poliklinik für Nuklearmedizin Leiter: Univ.-Prof. Dr. Mathias Schreckenberger

Klinik und Poliklinik für Nuklearmedizin Leiter: Univ.-Prof. Dr. Mathias Schreckenberger. 149 Tb radio-immunotherapy – advances of short-range alpha radiation and 4.1 h half-life demonstrated in vitro and in vivo . M. Miederer, J.Comor, S. Vanjes-Duric and GJ Beyer.

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Klinik und Poliklinik für Nuklearmedizin Leiter: Univ.-Prof. Dr. Mathias Schreckenberger

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  1. Klinik und Poliklinik für Nuklearmedizin Leiter: Univ.-Prof. Dr. Mathias Schreckenberger 149Tb radio-immunotherapy – advances of short-range alpha radiation and 4.1 h half-life demonstrated in vitro and in vivo M. Miederer, J.Comor, S. Vanjes-Duric and GJ Beyer

  2. Radiobiology of high LET Radition The extremely dense ionisations result in more lethal double strand breaks, which are not accessable to repair mechanisms (Locally multiply damaged site (LMDS)). • no dose-effect shoulder • no correlation with Oxygensaturation • dose rate less relevant

  3. Alpha track in relationtocancercells Tumor cell

  4. Antibody Penetration over time Confocal microscopy slices through the equator of LNCaP spheroids following incubation with 10 g/ml FITC-J591 and wash (3x). Incubation duration (min): 15 60 120 120 Ab penetration (cell diameters): Control:(10 g/ml FITC-HuM195) 1 2 3 Sgouros, et al

  5. Terbium-149 – a new Isotope for targeted cancer therapy ?

  6. Beyer et al 2001

  7. Comparision: 213Bi 149Tb

  8. In vitro system for investigation of single cell-kill potential of Terbium-149 Tb-149 – d9Mab bindingtogastriccancercells Monte Carlo simulation 149Tb 149Tb RIT 213Bi 213Bi RIT experiment Miederer et al 2003

  9. Comparision of theoretical and experimental single cell kill with Bi-213 and Tb-149 Conclusion: For Bi-213 and Tb-149 RIT theoryandexperimentareclose, however targetingneedstobeimprovedforsinglecell kill Miederer et al 2003

  10. In vivo systemforinvestigationofsinglecell-kill potential of Terbium-149 In vivo systemwithLymphomaxenograft 2 days after i.v. injection 1. High specificactivity 2. High affinityandinternalizingmonoclonalAntibody (Rituximab) Beyer et al 2004

  11. Radioactivity distribution in alpha-RIT with 149Tb-Rituximab Beyer et al 2004

  12. The retention of the long-lived daughter nuclides (149Eu, 145Sm) is identical and not influenced by the radioactive decay mode (alpha or EC) • All the daughter nuclides stabilizes themselve initially in the the unbound free Me3+ form, their excretion can be supported by suitable chelating ligands (EDTA for example) • 3. MIRDOSE model gives 400 mSv dose to a patient, for a 5 GBq149Tb-rituximab (weight factor 10 for a) Gamma spectra of the organs of the animals used in the study 120 days after injection for quantitative data analysis

  13. Dose-Limiting Toxicities after Cytarabine and 213Bi-HuM195 (Anti CD 33 in Leukemia) 2 GBq 213Bi-HuM195 appears save even in combination with chemotherapy Jurcic et al unpublished

  14. Current clinical application of Radioimmunotherapy with Y-90 In-111-CD66 dosimetry In-111-Zevalin dosimetry

  15. Acknowledgments Memorial Sloan-Kettering Cancer Center David A. Scheinberg, Joseph G. Jurcic, Michael McDevitt, Institute for Transuranium Elements Tuomo Nikula, Christos Apostolidis CERN, Geneva Gerd J. Beyer, Josef J Comor, Sanja Vranjes-Duric, ISOLDE Collaboration Nuclear Medicine/Radiochemistry National Cancer Institute Martin Brechbiel, Technical University Munich Reingard Senekowitsch-Schmidtke, Christof Seidl David E Charlton University Medical Center Geneva G. Künzi, O. Hartley, D. Soloviev, Franz Buchegger

  16. Cancer statistics SEER Database 2002-2006

  17. Experimental clinical application of radioimmunotherapy in solid tumors – Prostate Cancer In-111-J591 forprostatecancer, Pandit-Taskar, JNM 2008

  18. Experimental clinical application of radioimmunotherapy in solid tumors – renal cancer In-111-g250 forrenalcancer, Stillebroer, Cancer Imaging 2007

  19. clinical application of radiopeptides Therapy with Lutetium-177-DOTATATE PET imaging with Gallium-68-DOTATOC

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