In vitro screening for synergism of high-linear energy transfer 213Bi-radiotherapy with other therapeutic agents for the treatment of B-cell chronic lymphocytic leukemia.
BACKGROUND
External beam radiotherapy and beta-radioimmunotherapy (RIT) are effective treatments for lymphoid malignancies. The development of RIT with alpha-emitters is attractive, owing to the high (LET) nature and short path length of alpha particles allowing for higher tumor cell kill and lower toxicity to healthy tissues.


OBJECTIVE
The aim of this study was to assess the response of B-Cell chronic lymphocytic leukemia (B-CLL) cells in vitro after treatment with chemotherapy (cisplatin, fludarabine, doxorubicin, or vincristine) or other pharmaceuticals (colchicine, simvastatin, or cyclosporin A) in combination with (60)Co-gamma or (213)Bi-alpha-irradiation.


METHODS
(213)Bi was eluted from a (225)Ac generator. Apoptosis was scored by flow cytometric analysis of the cells stained with Annexin-V and 7 amino actinomycin D. Metabolic activity was assessed by a MTT assay.


RESULTS
The response induced by alpha- irradiation is systematically higher than the response induced by gamma-irradiation. The combination of drug treatment with alpha-irradiation induced a systematic, higher response, compared to treatment with drugs alone, even for the highest concentrations used. For all the drugs used in this study, synergism or additivity was demonstrated for the combination of drugs and radiotherapy with a stronger effect for alpha-particles.


CONCLUSIONS
The results of this in vitro study highlight a potential benefit of alpha-irradiation in combination with the drugs considered in this study.
Vandenbulcke
Katia
K
Department of Radiopharmacy, Ghent University, Ghent, Belgium.
Thierens
Hubert
H
De Vos
Filip
F
Philippé
Jan
J
Offner
Fritz
F
Janssens
Ann
A
Apostolidis
Christos
C
Morgenstern
Alfred
A
Bacher
Klaus
K
de Gelder
Virginie
V
Dierckx
Rudi A
RA
Slegers
Guido
G
D000512:Alpha Particles / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001729:Bismuth / Q000737:chemistry; D003131:Combined Modality Therapy; D004357:Drug Synergism; D005720:Gamma Rays / Q000627:therapeutic use*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D018499:Linear Energy Transfer; D011868:Radioisotopes
D011868:Radioisotopes; D001729:Bismuth