Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with 211At-MX35 F(ab')2.
Journal article, 2006
PURPOSE: To elucidate the therapeutic efficacy of alpha-radioimmunotherapy of ovarian cancer in mice. This study: (i) estimated the minimum required activity (MRA), giving a reasonable high therapeutic efficacy; and (ii) calculated the specific energy to tumor cell nuclei and the metastatic cure probability (MCP) using various assumptions regarding monoclonal-antibody (mAb) distribution in measured tumors. The study was performed using the alpha-particle emitter Astatine-211 (211At) labeled to the mAb MX35 F(ab')2. METHODS AND MATERIALS: Animals were inoculated intraperitoneally with approximately 1 x 10(7) cells of the cell line NIH:OVCAR-3. Four weeks later animals were treated with 25, 50, 100, or 200 kBq 211At-MX35 F(ab')2 (n = 74). Another group of animals was treated with a nonspecific mAb: 100 kBq 211At-Rituximab F(ab')2 (n = 18). Eight weeks after treatment the animals were sacrificed and presence of macro- and microscopic tumors and ascites was determined. An MCP model was developed and compared with the experimentally determined tumor-free fraction (TFF). RESULTS: When treatment was given 4 weeks after cell inoculation, the TFFs were 25%, 22%, 50%, and 61% after treatment with 25, 50, 100, or 200 kBq (211)At-MX35 F(ab')2, respectively, the specific energy to irradiated cell nuclei varying between approximately 2 and approximately 400 Gy. CONCLUSION: As a significant increase in the therapeutic efficacy was observed between the activity levels of 50 and 100 kBq (TFF increase from 22% to 50%), the conclusion was that the MRA is approximately 100 kBq (211)At-MX35 F(ab')2. MCP was most consistent with the TFF when assuming a diffusion depth of 30 mum of the mAbs in the tumors.
Statistical
Female
Antibodies
Data Interpretation
Treatment Outcome
Dose Fractionation
therapeutic use
secondary
Mice
Astatine
radiotherapy
Mice
Nude
therapeutic use
therapeutic use
Radiation Dosage
Ovarian Neoplasms
Inbred BALB C
Mice
methods
pathology
Radiopharmaceuticals
Monoclonal
Animals
Radioimmunotherapy
Author
Jörgen Elgqvist
University of Gothenburg
Håkan Andersson
University of Gothenburg
Peter Bernhardt
University of Gothenburg
Tom Bäck
University of Gothenburg
Ingela Claesson
University of Gothenburg
Ragnar Hultborn
University of Gothenburg
Holger Jensen
Bengt R Johansson
University of Gothenburg
Sture Lindegren
University of Gothenburg
Marita Olsson
Chalmers, Mathematical Sciences, Mathematical Statistics
University of Gothenburg
Stig Palm
University of Gothenburg
Elisabet Warnhammar Finnborg
University of Gothenburg
Lars Jacobsson
University of Gothenburg
International journal of radiation oncology, biology, physics
1879-355X (ISSN)
Vol. 66 4 1228-37Subject Categories
Cell and Molecular Biology
DOI
10.1016/j.ijrobp.2006.07.003
PubMed
17145538