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Selective High Affinity Ligands: A New Class of Targeting Agents for Cancer Imaging and Therapy

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Therapeutic Nuclear Medicine

Part of the book series: Medical Radiology ((Med Radiol Radiat Oncol))

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Abstract

Selective High Affinity Ligands (SHALs) are small molecule protein targeting agents that can be readily created using a combination of computational and experimental technologies. SHALs, which consist of two or three small molecule recognition elements linked together using lysine and miniPEGs, are designed to bind to a series of unique, neighboring cavities on the protein’s surface in a manner that mimics the process of molecular recognition employed by antibodies and other biomolecules. SHAL synthesis is highly modular. Individual recognition elements and linker lengths can be easily changed to improve binding or selectivity, effectors can be added to provide multiple mechanisms of toxicity, and tags can be attached to enable use as companion diagnostics, and imaging agents. Using this approach, a series of SHALs have been developed as therapeutics, diagnostics and imaging agents for B-cell lymphomas and related malignancies that overexpress the cell surface antigen HLA-DR10. Protein-, cell-, and tissue-based assays have confirmed that the molecules bind selectively and with high affinity (nM to pM Kd) to cells and tumor biopsy samples overexpressing HLA-DR10. In vivo, the SHALs have short blood and body clearance times as expected for small molecules and tissue biodistributions that are dictated by the types of compounds used as recognition elements. A number of SHALs have been shown to exhibit tumor selective cytotoxicity and show promise as imaging agents for non-Hodgkin’s lymphoma and other B-cell-derived malignancies.

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  1. Department of Applied Science, University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA

    Rod Balhorn

  2. Department of Chemistry and Biochemistry, California State University East Bay, Hayward, CA, 94542, USA

    Monique Cosman Balhorn

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Correspondence to Rod Balhorn .

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  1. THERANOSTICS Center for Molecular, Radiotherapy and Molecular Imaging, ENETS Center of Excellence, Bad Berka, Germany

    Richard P. Baum

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Balhorn, R., Balhorn, M.C. (2012). Selective High Affinity Ligands: A New Class of Targeting Agents for Cancer Imaging and Therapy. In: Baum, R. (eds) Therapeutic Nuclear Medicine. Medical Radiology(). Springer, Berlin, Heidelberg. https://doi.org/10.1007/174_2012_671

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