One of the major barriers toward the wide use of radiolabeled monoclonal antibodies (mAb) for molecular imaging and radionuclide therapy are the relatively high uptakes in non-tumor organs. Pre-targeting strategies present a promising approach to achieve improved sensitivity and specificity in small animal models, however, there are still a couple of limitations preventing them from being widely accepted for clinical use, including: 1) they are restricted to non-internalizing antibody, because the antibodies internalized into tumor cells are no longer available for ligation with RM; and 2) they have low tumor uptake, which consequently requires greater amounts of radionuclide to achieve high quality imaging and effective radiotherapy.In order to overcome these limitations, we have developed a novel universal pre-targeting strategy that substantially improves the sensitivity, specificity, and tumor uptake of radiotracer while with the broader scope of applicable mAbs (both internalizing and noninternalizing ones), thereby advancing current pre-targeting methods and facilitating their application within the biomedical sciences.
Description
In the previous pre-targeting strategies, the administrated radionuclide (with no tumor-targeting ligand) only provides low tumor uptake, which can be attributed to: 1) the administrated radionuclide itself has very low concentration on tumor; and 2) it is washed away from tumor very fast. The present invention relates to a dual-receptor pre-targeted (DRPT) molecular imaging and/or targeted drug delivery method, wherein an imaging label and/or therapeutic drug is integrated into a tumor-targeting small molecule that carries a moiety and also binds to the pre-administered tumor-specific antibody. Therefore, this small molecule, binding to both the pre-administered tumor-specific antibody and a biomarker on tumor, can be continuously trapped on tumor due to the generation of a slowclearing bioconjugate (ligation product between the small molecule and the preadministered tumor-specific antibody), and consequently resulting in increased sensitivity, increased specificity, improved signal to noise ratio, and greater applicability, as both internalizing and non-internalizing probes (e.g., antibodies) can be used.
Applications
Molecular Imaging
Radionuclide therapy
Biochemistry/Molecular Biology
Biomedical Sciences
Advantages
Increased sensitivity and specificity of molecular imaging agents
Improved tumor uptake Exceptional signal-to-noise ratio
Broadened scope of usable mAbs
Invention Readiness
In vivo experimentation completed
Data collected and analyzed
IP Status
https://patents.google.com/patent/US20190134239A1
