Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with {sup 211}At-MX35 F(ab'){sub 2}
- Department of Radiation Physics, Sahlgrenska Academy at Goeteborg University, Goeteborg (Sweden)
- Department of Oncology, Sahlgrenska Academy at Goeteborg University, Goeteborg (Sweden)
- PET and Cyclotron Unit, Rigshospitalet, Copenhagen (Denmark)
- Electron Microscopy Unit, Institute of Anatomy and Cell Biology, Goeteborg University, Goeteborg (Sweden)
- Bioinformatics Core Facility, Goeteborg University and Department of Mathematical Statistics, Chalmers University of Technology, Goeteborg (Sweden)
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 ({sup 211}At) labeled to the mAb MX35 F(ab'){sub 2}. Methods and Materials: Animals were inoculated intraperitoneally with {approx}1 x 10{sup 7} cells of the cell line NIH:OVCAR-3. Four weeks later animals were treated with 25, 50, 100, or 200 kBq {sup 211}At-MX35 F(ab'){sub 2} (n = 74). Another group of animals was treated with a nonspecific mAb: 100 kBq {sup 211}At-Rituximab F(ab'){sub 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 {sup 211}At-MX35 F(ab'){sub 2}, respectively, the specific energy to irradiated cell nuclei varying between {approx}2 and {approx}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 {approx}100 kBq {sup 211}At-MX35 F(ab'){sub 2}. MCP was most consistent with the TFF when assuming a diffusion depth of 30 {mu}m of the mAbs in the tumors.
- OSTI ID:
- 20850243
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 4 Vol. 66; ISSN IOBPD3; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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