Intraperitoneal Alpha-Radioimmunotherapy of Advanced Ovarian Cancer in Nude Mice using Different High Specific Activities

Jorgen Elgqvist, Daniel Ahlberg, Hakan Andersson, Holger Jensen, Bengt R Johansson, Helena Kahu, Marita Olsson, Sture Lindegren

Abstract


Background: The aim of this study was to investigate the therapeutic efficacy of advanced ovarian cancer in mice, using α-radioimmunotherapy with different high specific activities. The study was performed using the monoclonal antibody (mAb) MX35 F(ab')2 labeled with the α-particle emitter 211At.

Methods: Animals were intraperitoneally inoculated with ≥ 1 × 107 cells of the ovarian cancer cell line NIH:OVCAR-3. Four weeks later 9 groups of animals were given 25, 50, or 400 kBq 211At-MX35 F(ab')2 with specific activities equal to 1/80, 1/500, or 1/1200 (211At atom/number of mAbs) for every activity level respectively (n = 10 in each group). As controls, animals were given PBS or unlabeled MX35 F(ab')2 in PBS (n = 10  in each group). Eight weeks after treatment the animals were sacrificed and the presence of macroscopic tumors was determined by meticulous ocular examination of the abdominal cavity. Cumulated activity and absorbed dose calculations on tumor cells and tumors were performed using in house developed program. Specimens for scanning electron-microscopy analysis were collected from the peritoneum at the time of dissection.

Results: Summing over the different activity levels (25, 50, and 400 kBq 211At-MX35 F(ab')2) the number of animals with macroscopic tumors was 13, 17, and 22 (n = 30 for each group) for the specific activities equal to 1/80, 1/500, or 1/1200, respectively. Logistic-regression analysis showed a significant trend that higher specific activity means less probability for macroscopic tumors (P = 0.02).

Conclusions: Increasing the specific activity indicates a way to enhance the therapeutic outcome of advanced ovarian cancer, regarding macroscopic tumors. Further studies of the role of the specific activity are therefore justified.





doi:10.4021/wjon2010.05.208w


Keywords


Radioimmunotherapy; Alpha; 211At; Astatine; Specific activity; Intraperitoneal; Ovarian cancer; Mice

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