Abstract | PURPOSE: To determine whether the low-dose-rate alpha-particle-emitting radioimmunoconjugate (227)Th-1,4,7,10-p-isothiocyanato-benzyl-tetraazacyclododecane-1,4,7,10-tetraacetic acid ( DOTA)- rituximab can be used to inactivate lymphoma cells growing as single cells and small colonies. METHODS AND MATERIALS: CD20-positive lymphoma cell lines were treated with (227)Th-DOTA-rituximab for 1-5 weeks. To simulate the in vivo situation with continuous but decreasing supply of radioimmunoconjugates from the blood pool, the cells were not washed after incubation with (227)Th-DOTA-rituximab, but half of the medium was replaced with fresh medium, and cell concentration and cell-bound activity were determined every other day after start of incubation. A microdosimetric model was established to estimate the average number of hits in the nucleus for different localizations of activity. RESULTS: There was a specific targeted effect on cell growth of the (227)Th-DOTA-rituximab treatment. Although the cells were not washed after incubation with (227)Th-DOTA-rituximab, the average contribution of activity in the medium to the mean dose was only 6%, whereas the average contribution from activity on the cells' own surface was 78%. The mean dose rates after incubation with 800 Bq/mL (227)Th-DOTA-rituximab varied from 0.01 to 0.03 cGy/min. The average delay in growing from 10(5) to 10(7) cells/mL was 15 days when the cells were treated with a mean absorbed radiation dose of 2 Gy alpha-particle radiation from (227)Th-DOTA-rituximab, whereas it was 11 days when the cells were irradiated with 6 Gy of X-radiation. The relative biologic effect of the treatment was estimated to be 2.9-3.4. CONCLUSIONS:
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Authors | Jostein Dahle, Cecilie Krogh, Katrine B Melhus, Jørgen Borrebaek, Roy H Larsen, Yngve Kvinnsland |
Journal | International journal of radiation oncology, biology, physics
(Int J Radiat Oncol Biol Phys)
Vol. 75
Issue 3
Pg. 886-95
(Nov 01 2009)
ISSN: 1879-355X [Electronic] United States |
PMID | 19679402
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Murine-Derived
- Culture Media
- Immunoconjugates
- Organometallic Compounds
- thorium-227-DOTA-rituximab
- Rituximab
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Topics |
- Antibodies, Monoclonal
(therapeutic use)
- Antibodies, Monoclonal, Murine-Derived
- Cell Count
- Cell Line, Tumor
- Cell Proliferation
(radiation effects)
- Cell Size
- Culture Media
- Drug Screening Assays, Antitumor
- Humans
- Immunoconjugates
(therapeutic use)
- Lymphoma, B-Cell
(radiotherapy)
- Organometallic Compounds
(therapeutic use)
- Radioimmunotherapy
(methods)
- Radiotherapy Dosage
- Relative Biological Effectiveness
- Rituximab
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