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Research ArticleOncology

TAG-72–Targeted α-Radionuclide Therapy of Ovarian Cancer Using 225Ac-Labeled DOTAylated-huCC49 Antibody

Megan Minnix, Lin Li, Paul J. Yazaki, Aaron D. Miller, Junie Chea, Erasmus Poku, An Liu, Jeffrey Y.C. Wong, Russell C. Rockne, David Colcher and John E. Shively
Journal of Nuclear Medicine January 2021, 62 (1) 55-61; DOI: https://doi.org/10.2967/jnumed.120.243394
Megan Minnix
1Department of Molecular Imaging and Therapy, Beckman Research Institute, City of Hope, Duarte, California
2Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute, City of Hope, Duarte, California
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Lin Li
1Department of Molecular Imaging and Therapy, Beckman Research Institute, City of Hope, Duarte, California
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Paul J. Yazaki
1Department of Molecular Imaging and Therapy, Beckman Research Institute, City of Hope, Duarte, California
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Aaron D. Miller
1Department of Molecular Imaging and Therapy, Beckman Research Institute, City of Hope, Duarte, California
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Junie Chea
3Radiopharmacy, City of Hope Medical Center, Duarte, California
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Erasmus Poku
3Radiopharmacy, City of Hope Medical Center, Duarte, California
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An Liu
4Department of Radiation Oncology, City of Hope Medical Center, Duarte, California; and
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Jeffrey Y.C. Wong
4Department of Radiation Oncology, City of Hope Medical Center, Duarte, California; and
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Russell C. Rockne
5Division of Mathematical Oncology, Beckman Research Institute, City of Hope, Duarte, California
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David Colcher
1Department of Molecular Imaging and Therapy, Beckman Research Institute, City of Hope, Duarte, California
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John E. Shively
1Department of Molecular Imaging and Therapy, Beckman Research Institute, City of Hope, Duarte, California
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Abstract

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.

  • TAG-72
  • 225Ac
  • radioimmunotherapy
  • ovarian cancer

Footnotes

  • Published online Jul. 3, 2020.

  • © 2021 by the Society of Nuclear Medicine and Molecular Imaging.
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Journal of Nuclear Medicine: 62 (1)
Journal of Nuclear Medicine
Vol. 62, Issue 1
January 1, 2021
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TAG-72–Targeted α-Radionuclide Therapy of Ovarian Cancer Using 225Ac-Labeled DOTAylated-huCC49 Antibody
Megan Minnix, Lin Li, Paul J. Yazaki, Aaron D. Miller, Junie Chea, Erasmus Poku, An Liu, Jeffrey Y.C. Wong, Russell C. Rockne, David Colcher, John E. Shively
Journal of Nuclear Medicine Jan 2021, 62 (1) 55-61; DOI: 10.2967/jnumed.120.243394

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TAG-72–Targeted α-Radionuclide Therapy of Ovarian Cancer Using 225Ac-Labeled DOTAylated-huCC49 Antibody
Megan Minnix, Lin Li, Paul J. Yazaki, Aaron D. Miller, Junie Chea, Erasmus Poku, An Liu, Jeffrey Y.C. Wong, Russell C. Rockne, David Colcher, John E. Shively
Journal of Nuclear Medicine Jan 2021, 62 (1) 55-61; DOI: 10.2967/jnumed.120.243394
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Keywords

  • TAG-72
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