Intraperitoneally (i.p.) administered radiolabeled monoclonal antibodies have been tested in several clinical trials, often with promising results, but never proven curative. Methods: We have previously presented simulations of clinically relevant amounts of i.p. 90Y-mAb treatments of minimal disease and shown that such treatments are unlikely to eradicate microtumors. Our previous model simulated the kinetics of intraperitoneally infused radiolabeled mAb in man, and showed the benefit of instead using alpha-emitters such as 211At. In the current work, we introduce also penetration of mAbs into tissue of microtumors with radii up to 400 μm. Calculations were performed by dynamic simulation using the software STELLA. In order to determine the radiation dose distribution in non-vascularized microtumors of various sizes following i.p. [211At] α-RIT an in-house developed Monte Carlo program was used for microdosimetry. Our aim was to find methods that optimize the therapy for as large tumor size interval as possible. Results: Our results show that high-specific-activity radiolabeled mAbs that are bound to a tumor surface will penetrate slowly compared to the half-lives of 211At and shorter-lived radionuclides. Inner-core cells of tumors with radii >100 μm may therefore not be sufficiently irradiated. For lower specific activities, the penetration rate and the dose distribution will be more favorable for such tumors, but the dose to smaller microtumors and single cells will be low. Conclusion: Our calculations show that addition of a boost with unlabeled mAb 1–5 hours following therapy results in sufficient absorbed doses to both single cells and throughout microtumors up to ~300 μm radius. This should be valid also for other high-affinity mAbs and short-lived alpha-emitters.
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