RT Journal Article SR Electronic T1 TAG-72–Targeted α-Radionuclide Therapy of Ovarian Cancer Using 225Ac-Labeled DOTAylated-huCC49 Antibody JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 55 OP 61 DO 10.2967/jnumed.120.243394 VO 62 IS 1 A1 Megan Minnix A1 Lin Li A1 Paul J. Yazaki A1 Aaron D. Miller A1 Junie Chea A1 Erasmus Poku A1 An Liu A1 Jeffrey Y.C. Wong A1 Russell C. Rockne A1 David Colcher A1 John E. Shively YR 2021 UL http://jnm.snmjournals.org/content/62/1/55.abstract 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.