In vitro evaluation of 213Bi-rituximab versus external gamma irradiation for the treatment of B-CLL patients: Relative biological efficacy with respect to apoptosis induction and chromosomal damage by the micronucleus assay


Katia Vandenbulcke1, Filip De Vos2, Fritz Offner3, Jan Philippe4, Christos Apostolidis5, Roger Molinet5, Tuomo K Nikula5, Klaus Bacher6, Virginie de Gelder6, Anne Vral6, Christophe Lahorte1, Hubert Thierens6, Rudi A. Dierckx2, and Guido Slegers1. (1) Department of Radiopharmacy, University of Gent, Gent, Belgium, (2) Department of Nuclear Medicine, Gent University Hospital, Gent, Belgium, (3) Department of Hematology, University of Gent, Gent, Belgium, (4) Department of Clinical Chemistry, University of Gent, Gent, Belgium, (5) Nuclear Chemistry, European Commission, JRC, Institute for Transuranium Elements, B.O.Box 2340, 76125 Karlsruhe, Germany, (6) Department of Radiation Physics, University of Gent, Gent, Belgium
The radioimmunotherapy (RIT) with alpha-emitters is attractive because of the high LET and short path length allowing higher tumor cell kill and lower toxicity to healthy tissues. We assessed the relative biological efficacy (RBE) of alpha RIT (in vitro) compared with external gamma irradiation with respect to induction of apoptosis in B-CLL and induction of chromosomal damage in B and T lymphocytes. The dose range experiments demonstrated 213Bi-anti-CD20 was more effective than equivalent doses by external gamma irradiation to introduce apoptosis. The RBE for induction of apoptosis in B-CLL ranged from 2.2 at 2 Gy to 1 at 10 Gy. The micronucleus yield on lymphocytes was measured to assess the late toxicity by induction of chromosomal instability. While gamma-radiation induced a steady increase in micronucleus yields in B and T cells, the damage inflicted by 213Bi was more dramatic with RBE ranging from 5 to 2 between 0.1 Gy and 2 Gy. In contrast to gamma irradiation, 213Bi inhibited forced mitosis almost completely at 2 Gy.