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 were thought to be inappropriate for the treatment of solid tumors where 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 anti-tumor effects at the tumor vascular level, while 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 actinium-225 to target TAG-72 positive xenografts in a murine model of ovarian cancer. Results: Actinium-225 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 to the untreated control. Additionally, a multi-treatment 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 to 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.
- Genitourinary
- Monoclonal Antibodies
- Oncology: GYN
- PET
- Radiobiology/Dosimetry
- Radioimmunoimaging
- Radionuclide Therapy
- TAG72
- actinium-225
- ovarian cancer
- radioimmunotherapy
- Copyright © 2020 by the Society of Nuclear Medicine and Molecular Imaging, Inc.