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

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 a-particle emitter Astatine-211 (At-211) labeled to the mAb MX35 F(ab')(2). Methods and Materials: Animals were inoculated intraperitoneally with similar to 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 At-211-MX35 F(ab')(2) (n = 74). Another group of animals was treated with a nonspecific mAb: 100 kBq At-211-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 At-211-MX35 F(ab')2, respectively, the specific energy to irradiated cell nuclei varying between similar to 2 and similar to 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 similar to 100 kBq At-211-MX35 F(ab')(2). MCP was most consistent with the TFF when assuming a diffusion depth of 30 mu m of the mAbs in the tumors. (c) 2006 Elsevier Inc.