PT - JOURNAL ARTICLE AU - Megan Minnix AU - Lin Li AU - Paul J. Yazaki AU - Aaron D. Miller AU - Junie Chea AU - Erasmus Poku AU - An Liu AU - Jeffrey Y.C. Wong AU - Russell C. Rockne AU - David Colcher AU - John E. Shively TI - TAG-72–Targeted α-Radionuclide Therapy of Ovarian Cancer Using <sup>225</sup>Ac-Labeled DOTAylated-huCC49 Antibody AID - 10.2967/jnumed.120.243394 DP - 2021 Jan 01 TA - Journal of Nuclear Medicine PG - 55--61 VI - 62 IP - 1 4099 - http://jnm.snmjournals.org/content/62/1/55.short 4100 - http://jnm.snmjournals.org/content/62/1/55.full SO - J Nucl Med2021 Jan 01; 62 AB - Radioimmunotherapy, an approach using radiolabeled antibodies, has had minimal success in the clinic with several β-emitting radionuclides for the treatment of ovarian cancer. Alternatively, radioimmunotherapy with α-emitters offers the advantage of depositing much higher energy over shorter distances but was thought to be inappropriate for the treatment of solid tumors, for which antibody penetration is limited to a few cell diameters around the vascular system. However, the deposition of high-energy α-emitters to tumor markers adjacent to a typical leaky tumor vascular system may have large antitumor effects at the tumor vascular level, and their reduced penetration in normal tissue would be expected to lower off-target toxicity. Methods: To evaluate this concept, DOTAylated-huCC49 was labeled with the α-emitter 225Ac to target tumor-associated glycoprotein 72–positive xenografts in a murine model of ovarian cancer. Results: 225Ac-labeled DOTAylated-huCC49 radioimmunotherapy significantly reduced tumor growth in a dose-dependent manner (1.85, 3.7, and 7.4 kBq), with the 7.4-kBq dose extending survival by more than 3-fold compared with the untreated control. Additionally, a multitreatment regime (1.85 kBq followed by 5 weekly doses of 0.70 kBq for a total of 5.4 kBq) extended survival almost 3-fold compared with the untreated control group, without significant off-target toxicity. Conclusion: These results establish the potential for antibody-targeted α-radionuclide therapy for ovarian cancer, which may be generalized to α-radioimmunotherapy in other solid tumors.