SUMMARY OF INVENTION
Owing to their high specificity and affinity, the use of radiolabeled antibodies to target cancer cells in diagnostic and therapeutic settings has been increasingly explored in the clinic. Due to antibodies’ relatively slow pharmacokinetics, however, conjugated radioisotopes with long physical half-lives are required to allow the antibody sufficient time to localize to the tissue and clear from the body prior to imaging or treatment. This often necessitates the use of high radiation doses to patients and can result in undesirable activity at nontarget organs.
To address these limitations, investigators at MSK have developed a novel method of pretargeting PET imaging and radioimmunotherapy based on biorthogonal Diels-Alder click chemistry. By covalently attaching transcyclooctene (TCO) to a targeting antibody and radiolabeling a NOTA-modified tetrazine with e.g., 64Cu-radionuclides, investigators produced high contrast images while dramatically reducing nontarget radiation doses to patients. Briefly, the pretargeting system enables:
- Injection of TCO labeled antibody
- Slow clearance and accumulation of the antibody at tumor site
- Injection of the radioligand, which localizes to the antibody by in vivo click chemistry
- Rapid clearance of unbound radioligand for high contrast imaging and/or targeted radiotherapy
- Modularity of the system allows the TCO moiety to be attached to any antibody, whereas tetrazine-based radioligand enables the creation of various compatible radioisotopes.
- This technology produces high tumor-to-background contrast images while reducing the required dose of radioisotopes, resulting in less off-target activity.
This novel invention may be a more effective and safer alternative to ImmunoPET/immunoSPECT imaging and radioimmunotherapy with long-lived isotopes.
STAGE OF DEVELOPMENT
Expected to enter clinic by year-end 2022
National US Patent 11,135,320 issued on October 5th, 2021; Continuation application 17/464,472 currently pending.
- Jason Lewis, PhD, Emily Tow Jackson Chair in Oncology; Vice Chair for Research, Department of Radiology; Chief, Radiochemistry & Imaging Sciences Service; and Director of Radiochemistry & Molecular Imaging Probe Core Facility, MSK
- Thomas Reiner, PhD, Executive Director, Radioligand Therapy, Novartis. Former Laboratory Head, MSK
James Delorme, Ph.D.
E-mail: [email protected]