Novel Cathepsin Targeted Agents for Molecular Imaging of Cancer and Atherosclerosis

Blum Galia, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research

Cathepsin Targeted  Computed Tomography X-Ray Contrast Agents for Molecular Imaging of Cancer


We focused on the development, synthesis and characterization of new classes of computed tomography (CT) contrast reagents targeted to the cysteine cathepsin proteases, based on the activity based probe (ABP) methodology. These novel probes enable detection of the elevated cathepsin activity within cancerous tissue using a CT instrument.

X-ray CT instruments are among the most available, efficient and cost-effective imaging modalities in hospitals. The field of CT molecular imaging agents is emerging relying mainly on detection of gold and bismuth nanoparticles, iodine and gadolinium labeled compounds. However, the low sensitivity of CT scanners to contrast reagents makes this a challenging task.

We have generated two libraries of probes, one labeled with iodine and the other with gold nanoparticles. Both libraries target and covalently bind to the  through a uniquemoiety, consisting of recognition peptide sequence and an electrophilic moiety for binding. After chemical and biochemical evaluations; we selected the most potent and stable probes of each library to proceed to non-invasive imaging in cancer mice models. CT contrast from the tumor could be detected after injection of targeted probes from both libraries, The specific signal increased over time and was significant higher compared to non-targeted particle controls. Contrast agent concentrations and sub-cellular localization within the tumor cells was detected using transmission electron microscopy (TEM). Thus, we were able to generate CT molecular imaging probes that report on cathepsin activity within tumors bearing mice.





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Shoshana Keynan
VP, Head of Business Development, Healthcare
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