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Design of Radiolabeled Peptide Radiopharmaceuticals

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Molecular Imaging and Targeted Therapy

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Abstract

Peptides are short chains of amino acids (AA) containing less than 40–50 AAs. Twenty AAs appear in the genetic code and are considered as “standard” alpha AAs (or proteinogenic AAs). The peptide bond is an amide type of covalent chemical bond linking two consecutive α-amino acids. Compared with larger proteins and antibodies, peptides can penetrate and diffuse further into the tumor tissue because of their low molecular mass, and relatively small size. Since 1994, following the approval of 111In-DTPA-octreotide (Octreoscan) for imaging somatostatin receptor (SSTR) positive neuroendocrine tumors (NETs), several radiolabeled peptide drug conjugates (RPDC) have been approved for routine clinical use for PET imaging and targeted radionuclide therapy (TRT). Except for radiohalogens (18F, 123/124/131I), most PRPs for imaging and therapy are based on metallic radionuclides, such as 111In, 64Cu, 68Ga, 90Y, 177Lu, and 225Ac. The chemical components of a target-specific RPDC may have individual components such as targeting vehicle (peptide), spacer and/or linker, a bifunctional chelator (BFC), and radionuclide. The target specificity and in vivo stability of bioactive peptides can be improved by cyclization and substitution of non-natural AAs. This chapter provides a broad overview of the design and development of RPDCs for imaging and TRT of cancers expressing different peptide receptors.

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  1. Emeritus of Radiochemistry and Radiopharmacy in Radiology, Weill Cornell Medicine, Cornell University, New York, NY, USA

    Shankar Vallabhajosula

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  1. Shankar Vallabhajosula
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Correspondence to Shankar Vallabhajosula .

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Vallabhajosula, S. (2023). Design of Radiolabeled Peptide Radiopharmaceuticals. In: Molecular Imaging and Targeted Therapy. Springer, Cham. https://doi.org/10.1007/978-3-031-23205-3_20

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  • DOI: https://doi.org/10.1007/978-3-031-23205-3_20

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