Damon Runyon Researchers

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Paul C. Klauser, PhD

Radiopharmaceuticals, or drugs that contain radioactive forms of chemical elements, have transformed cancer diagnosis and treatment. Radioactive copper and manganese, for example, play a crucial role in PET imaging, while radioactive lutetium is used to deliver targeted radiation to cancer cells. While these radiometals have tremendous potential, however, their application is hindered by a lack of efficient “chelators,” or molecules that can securely bind radiometals in the human body. Computational protein design offers a solution by engineering protein-based chelators optimized for radiometal coordination, stability, and biocompatibility. Using advanced protein modeling, Dr. Klauser will develop chelators for radiometals, improving diagnostic imaging and advancing lutetium-based radiotherapies. While this work is applied to HER2-positive gastric cancer, these strategies have broad applications across various cancer types, ultimately enhancing precision oncology and expanding radiopharmaceutical utility.

This research develops a computational strategy to design stable, compact metal-binding proteins for radiopharmaceuticals, enabling fusion with therapeutic antibodies. Using diffusion models, such as RFdiffusion, thousands of protein backbones are generated for metals like copper and manganese. Sequences are assigned via ProteinMPNN, filtered for stability and binding with AlphaFold 3. For rare lanthanides, symmetric duplication of known binding motifs is used. This approach streamlines the discovery of stable scaffolds for radiopharmaceutical applications.

Project title: "Generative artificial intelligence enabling next-generation radiopharmaceuticals"
Institution: Memorial Sloan Kettering Cancer Center
Award Program: Quantitative Biology Fellow
Sponsor(s) / Mentor(s): Jason S. Lewis, PhD, and Caleb A. Lareau, PhD
Cancer Type: All Cancers
Research Area: Experimental Therapeutics