In vitro cytotoxicity of low-dose-rate radioimmunotherapy by the alpha-emitting radioimmunoconjugate Thorium-227-DOTA-rituximab.

Full 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: The low-dose-rate radioimmunoconjugate (227)Th-DOTA-rituximab is suitable for inactivation of single lymphoma cells and small colonies of lymphoma cells.

Author information

Author/s: Dahle, Jostein (J); Krogh, Cecilie (C); Melhus, Katrine B (KB); Borrebaek, Jørgen (J); Larsen, Roy H (RH); Kvinnsland, Yngve (Y);

Affiliation: Department of Radiation Biology, Norwegian Radium Hospital, Montebello, Oslo, Norway. jostein.dahle(-atsign-)rr-research.no

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys), published in United States. (Language: eng)

Reference: 2009-Nov; vol 75 (issue 3) : pp 886-95

Dates: Created 2009/10/05; Completed 2009/10/20;

PMID: 19679402, status: MEDLINE (last retrieved date: 10/20/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Humans
Immunoconjugates - therapeutic use
Lymphoma, B-Cell - radiotherapy
Organometallic Compounds - therapeutic use
Radioimmunotherapy - methods
Radiotherapy Dosage
Relative Biological Effectiveness

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Antibodies, Monoclonal (0) ; Culture Media (0) ; Immunoconjugates (0) ; Organometallic Compounds (0) ; thorium-227-DOTA-rituximab (0)

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