Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with 211At-MX35 F(ab′)2

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Abstract

Purpose: To elucidate the therapeutic efficacy of α-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 α-particle emitter Astatine-211 (211At) labeled to the mAb MX35 F(ab′)2. Methods and Materials: Animals were inoculated intraperitoneally with ∼1 × 107 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 211At-MX35 F(ab′)2, respectively, the specific energy to irradiated cell nuclei varying between ∼2 and ∼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 ∼100 kBq 211At-MX35 F(ab′)2. MCP was most consistent with the TFF when assuming a diffusion depth of 30 μm of the mAbs in the tumors. © 2006 Elsevier Inc. All rights reserved.

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Elgqvist, J., Andersson, H., Bernhardt, P., Bäck, T., Claesson, I., Hultborn, R., … Jacobsson, L. (2006). Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with 211At-MX35 F(ab′)2. International Journal of Radiation Oncology Biology Physics, 66(4), 1228–1237. https://doi.org/10.1016/j.ijrobp.2006.07.003

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