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-Radioimmunotherapy of Intraperitoneally Growing OVCAR-3 Tumors of Variable Dimensions: Outcome Related to Measured Tumor Size and Mean Absorbed Dose

¹ Department of Radiation Physics, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden; ² Department of Oncology, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden; ³ PET and Cyclotron Unit, Rigshospitalet, Copenhagen, Denmark; ⁴ The Electron Microscopy Unit, Institute of Anatomy and Cell Biology, Göteborg University, Göteborg, Sweden; and ⁵ Bioinformatics Core Facility, Göteborg University, and Department of Mathematical Statistics, Chalmers University of Technology, Göteborg, Sweden

Correspondence: For correspondence or reprints contact: Jörgen Elgqvist, PhD, Department of Radiation Physics, The Sahlgrenska Academy at Göteborg University, SE-413 45 Göteborg, Sweden. E-mail: jorgen.elgqvist{at}radfys.gu.se

The purpose of this work was to (a) investigate the efficacy of radioimmunotherapy using ²¹¹At-MX35 F(ab')₂ or ²¹¹At-Rituximab F(ab')₂ (nonspecific antibody) against differently advanced ovarian cancer in mice; (b) image the tumor growth on the peritoneum; and (c) calculate the specific energy and mean absorbed dose to tumors and critical organs. Methods: Two experiments with 5-wk-old nude mice (n = 100 + 93), intraperitoneally inoculated with 1 x 10⁷ NIH:OVCAR-3 cells, were done. At either 1, 3, 4, 5, or 7 wk after inoculation animals were intraperitoneally treated with 400 kBq ²¹¹At-MX35 F(ab')₂ (n = 50 + 45), 400 kBq ²¹¹At-Rituximab F(ab')₂ (n = 25 + 24), or unlabeled Rituximab F(ab')₂ (n = 25 + 24). At the time of treatment 29 animals were sacrificed and biopsies were taken for determination of tumor sizes using scanning electron microscopy (SEM). Eight weeks after each treatment the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. The specific energy and mean absorbed dose to tumors were calculated. The activity concentration was measured in critical organs and abdominal fluid. Results: When given treatment 1, 3, 4, 5, or 7 wk after cell inoculation the tumor-free fraction (TFF) was 95%, 68%, 58%, 47%, 26%, and 100%, 80%, 20%, 20%, and 0% when treated with ²¹¹At-MX35 F(ab')₂ or ²¹¹At-Rituximab F(ab')₂, respectively. The SEM images revealed maximum tumor radius of 30 µm 1 wk after cell inoculation, increasing to 340 µm at 7 wk. Specific energy to cell nuclei varied between 0 and 540 Gy, depending on assumptions regarding activity distribution and tumor size. The mean absorbed dose to thyroid, kidneys, and bone marrow was 35, 4, and 0.3 Gy, respectively. Conclusion: Treatment with ²¹¹At-MX35 F(ab')₂ or ²¹¹At-Rituximab F(ab')₂ resulted in a TFF of 95%–100% when the tumor radius was 30 µm. The TFF was decreased (TFF 20%) for ²¹¹At-Rituximab F(ab')₂ when the tumor radius exceeded the range of the -particles. The specific antibody gave for these tumor sizes a significantly better TFF, explained by a high mean absorbed dose (>22 Gy) from the activity bound to the tumor surface and probably some contribution from penetrating activity.

Key Words: ovarian cancer • radioimmunotherapy • dosimetry • astatine • MX35

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