Radioligands for pretargeted pet imaging and methods of their therapeutic use

Abstract

Described herein are Tz / TCO-based pretargeting strategies using an Al[18F]-NOTA-labeled tetrazine radioligand. This imaging strategy enables delineation of cancer at earlier time points compared to other imaging strategies and further decreases the radiation dose to healthy tissues compared to directly labeled antibodies. Al-based 18F imaging of small molecules, such as tetrazine, has not been previously achieved due to the decomposition of tetrazine during radiofluorination. Radiofluorination is advantageous over other radiolabeling methods because, in addition to having a shorter half-life, 18F is more readily available to produce and therefore integrated into hospital workflows.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to and the benefit of, and incorporates herein by reference in its entirety, U.S. Provisional Patent Application No. 62 / 159,763, filed May 11, 2015.GOVERNMENT SUPPORT[0002]This invention was made with government support under grant 1K99 CA178205-01 awarded by the National Institutes of Health (NIH) / National Cancer Institute (NCI) and grants P30 CA08748, K25 EB016673, TR; R00 CA1440138, BMZ; 2R42CA128362, awarded by the National Institutes of Health (NIH). The government has certain rights in the invention.FIELD OF THE INVENTION[0003]This invention relates generally to pretargeted positron emission tomography (PET) imaging of cancer. In particular embodiments, the invention relates to radioligands for pretargeted PET imaging of cancer (e.g., colorectal, pancreatic, etc.).BACKGROUND[0004]Over the past 25 years, antibodies have emerged as effective vectors for the sensitive and specific delivery of radioisoto...

AI Technical Summary

Benefits of technology

The patent describes imaging techniques for cancer using a special molecule called tetrazine and a radionuclide called 64Cu. This approach allows for faster excretion of the excess molecule through the kidneys and bladder, resulting in lower radiation doses to healthy tissues compared to other imaging methods. The patent also describes the development of an anti-CA19.9 antibody and a 18F-labeled tetrazine molecule for the visualization of BxPC3 pancreatic cancer xenografts. The results show that this approach effectively delineates tumor mass with high activity concentrations. Overall, the patent offers a more effective and safer way to diagnose and treat cancer.

Problems solved by technology

Al-based 18F imaging of small molecules, such as tetrazine, has not been previously achieved due to the decomposition of tetrazine during radiofluorination.

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