TY - JOUR T1 - Therapeutic Efficacy and Tumor Dose Estimations in Radioimmunotherapy of Intraperitoneally Growing OVCAR-3 Cells in Nude Mice with <sup>211</sup>At-Labeled Monoclonal Antibody MX35 JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1907 LP - 1915 VL - 46 IS - 11 AU - Jörgen Elgqvist AU - Håkan Andersson AU - Tom Bäck AU - Ragnar Hultborn AU - Holger Jensen AU - Börje Karlsson AU - Sture Lindegren AU - Stig Palm AU - Elisabet Warnhammar AU - Lars Jacobsson Y1 - 2005/11/01 UR - http://jnm.snmjournals.org/content/46/11/1907.abstract N2 - The purpose of this study was to investigate the therapeutic efficacy of—and to estimate the absorbed dose to—tumor cells from radioimmunotherapy (RIT) in an ovarian cancer model using the α-particle–emitting nuclide 211At labeled to monoclonal antibody (mAb) MX35. Previous studies on mAb MOv18 did not allow for dosimetry because of antigen shedding in vitro. Methods: Five-week-old female nude BALB/c nu/nu mice were inoculated intraperitoneally with 1 × 107 cells of the human tumor cell line OVCAR-3. Three weeks later, the animals were given approximately 400, 800, or 1,200 kBq of 211At-labeled mAb MX35 intraperitoneally. As controls, one group of animals was injected with unlabeled mAb and another group was injected with phosphate-buffered saline (PBS). Another group was given approximately 400 kBq of 211At labeled to the previously investigated mAb MOv18 for efficacy comparison. Two months after treatment, the animals were sacrificed and the presence of macroscopic and microscopic tumors, as well as ascites, was determined. The absorbed dose to tumor cells on the peritoneal surface was estimated in terms of the sum of a specific and a nonspecific contribution. The specific contribution, arising from mAbs binding to the antigenic sites on the cell membrane, was calculated using a dynamic compartment model developed in-house and Monte Carlo software. The model used as input values the number of mAbs injected into the abdominal cavity, NmAb, the specific activity, Asp, the association rate constant, kon, and the maximal number of mAbs bound per cell, Bmax—all determined by in vitro experiments. This specific component of the absorbed dose was calculated for assumed cell cluster sizes with radii of 25, 50, and 100 μm. The nonspecific contribution to the absorbed dose was derived from unbound mAbs freely circulating in the abdominal cavity, also using the Monte Carlo software. Results: In the control groups given unlabeled MX35 or PBS, all 18 animals had ascites, 6 of 9 animals in each group had macroscopic tumors, and all animals had microscopic growth. In the 3 groups given different amounts of 211At-MX35, only 3 of 25 animals developed ascites. None of these animals had any sign of macroscopic tumors, but 8 had microscopic growth. In the group given 211At-MOv18, no animals had ascites or macroscopic tumors, but 3 of 10 animals had microscopic tumors. After injecting 400 kBq of 211At-MX35, the absorbed dose due to specific binding, for a cell cluster with a radius of 50 μm, ranged from 413 to 223 Gy between 0- and 45-μm distance from the cluster center, assuming a homogeneous distribution of 211At-MX35 in the cluster. The contribution from unbound 211At-MX35 and 211At-MX35 only distributed on the cluster surface, for this cluster size, ranged from 7 to 14 Gy and from 29 to 94 Gy, between 0- and 45-μm distance from the cluster center, respectively. The calculated total absorbed doses are in a clinically relevant range and were effective as verified in the nude mice with subclinical intraperitoneal growth of OVCAR-3 cells. Conclusion: 211At-MX35 injected intraperitoneally exhibits a high efficacy when treating micrometastatic growth of the ovarian cancer cell line OVCAR-3 on the peritoneum of nude mice. ER -