SUMMARY OF INVENTION
Antibody-based PET imaging can allow for highly specific imaging of tumors, and potentially indicate patients who may be amenable to treatment with targeted antibody-based therapies. Zirconium-89 is a radioisotope with a relatively long half-life (78 hours) that matches the half-life of antibodies in the blood (50-90 hours), and it is ideal for antibody-based PET imaging. However, when the commonly used chelator DFO is used to radiolabel antibodies with 89Zr, there is an accumulation of radioactivity in the bone, suggesting that the 89Zr is being released in vivo. This accumulation of radioactivity in the bone, a non-target tissue, is unfavorable for patients.
MSK investigators have developed a more robust chelator for 89Zr which could reduce the dose of radiation to nontarget tissues. This chelator, called HOPO, shows efficient binding of 89Zr. In in vivo models of breast cancer, antibodies conjugated to HOPO and radiolabeled with 89Zr show favorable tumor to organ contrast and very low bone uptake.
- Potentially safer chelator for 89Zr antibody-based PET imaging, with decreased non-specific accumulation of radiation in healthy bone tissues compared to the conventionally used chelator DFO
- Allows for favorable tumor-to-organ contrast with 89Zr-labeled antibodies, which facilitates improved PET imaging
- Potential for expanded identification of patients eligible for treatment with targeted antibody therapies
This bifunctional ligand could be conjugated to any antibody and radiolabeled with 89Zr, for purposes of PET imaging. Such a radiolabeled antibody could enable the evaluation of all malignant lesions in the body (vs. a single lesion by biopsy) when evaluating whether a patient is a candidate for targeted therapy treatment. Therefore, this could allow for identification of additional patients amenable for treatment with targeted therapy. With a more favorable safety profile than the commonly used chelator DFO, its market opportunity could be significant.
Deri M. et al., p‑SCN-Bn-HOPO: A Superior Bifunctional Chelator for 89Zr ImmunoPET. Bioconjugate Chemistry, 2015 Dec 16; 26(12):2579-91. (PubMed ID: 26550847)
STAGE OF DEVELOPMENT
PCT application filed in September 2016
Jason Lewis, PhD, Director, Center for Molecular Imaging and Nanotechnology, Sloan Kettering Institute, MSK
Eileen Flowers, PhD