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Double Targeting Ligands Identifies and Treats Prostate Cancer

By Medimaging International staff writers
Posted on 27 Sep 2017
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Image: Targeted theranostic therapy using RPS-027 (Photo courtesy of JM Kelly / Weill Cornell Medicine).
Image: Targeted theranostic therapy using RPS-027 (Photo courtesy of JM Kelly / Weill Cornell Medicine).
A new study describes how a theranostic approach can precisely identify prostate cancer tumors for targeted radiotherapy (RT), while sparing healthy cells and reducing side effects.

Developed by researchers at Weill Cornell Medicine (New York, NY, USA), the new approach utilizes a single molecule designed to bind two proteins with differing affinities--prostate-specific membrane antigen (PSMA) and human serum albumin--in an effort to optimize specific tumor localization and enhance targeted alpha radionuclide therapy. The double targeting ligand, RPS-027, was tested in mouse models of human prostate cancer using the radiohalogen 211At.

The results, as assessed via positron emission tomography/computed tomography (PET/CT), showed high tumor uptake, reduced kidney uptake, and very favorable tissue distribution. When compared to existing ligands proposed for targeted therapy of prostate cancer, RPS-027 has tumor-to-tissue ratios that predicted a significant reduction in side effects during therapy, suggesting that dual targeting ligands could serve as the next-generation radiopharmaceuticals for targeted alpha therapy. The study was published in the September 2017 issue of The Journal of Nuclear Medicine.

“We believe that our double targeting ligands are the first PSMA ligands designed to make use of the blood pool as a ‘safe zone’ reservoir to protect sensitive organs and tissues from off-target effects of alpha irradiation and, simultaneously, to reduce kidney localization, while maintaining excellent tumor targeting,” said senior author Professor John Babich, PhD. “If our strategy can be applied successfully to other therapeutic targeting agents, we could expect an expansion in the use of targeted alpha therapy in the not-too-distant future.”

Targeted alpha-particle therapy is a radionuclide therapy that employs radioactive substances, which undergo alpha decay to treat diseased tissue at close proximity. It has the potential to provide highly targeted treatment, especially to microscopic tumor cells such as in leukemias, lymphomas, gliomas, melanoma, and peritoneal carcinomatosis. Appropriate radionuclides can be chemically bound to a targeting biomolecule, which carries the combined radiopharmaceutical to a specific treatment point.

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