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Pretargeted Radiopharmaceutical Therapy

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Radiopharmaceutical Therapy

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Abstract

Radioimmunotherapy (RIT) has long stood as a promising approach to radiopharmaceutical therapy (RPT). However, the relatively slow pharmacokinetic profile of full-length radioimmunoconjugates can lead to toxic radiation doses to off-target organs. In pretargeted radioimmunotherapy (PRIT), the antibody and the radionuclide are decoupled, the former is administered hours to days ahead of the latter, and the two components undergo a selective ligation at the tumor site. Several approaches to PRIT have been developed over the past three decades, each based on a pair of moieties—a “molecular couple”—that react with one another in vivo with high specificity and affinity. All PRIT strategies follow the same general steps. First, the antibody bearing one half of the molecular couple is administered. Then, after the antibody has cleared from the blood and non-target organs, a radiolabeled variant of the complementary half of the molecular couple is injected. This radioligand, by design a small molecule, travels through the body quickly and either undergoes a ligation with the immunoconjugate at the tumor or is rapidly excreted. This approach is designed to deliver high radiation doses to tumor tissue while simultaneously minimizing the irradiation of healthy organs. In this chapter, we will provide examples of the use of in vivo pretargeting in nuclear medicine and discuss the most common approaches to in vivo pretargeting, including strategies based on streptavidin and biotin, bispecific antibodies, complementary oligonucleotides, and biorthogonal click chemistry.

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Authors and Affiliations

  1. Department of Chemistry, Hunter College, City University of New York, New York, NY, USA

    Outi M. Keinänen & Brian M. Zeglis

  2. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Outi M. Keinänen & Brian M. Zeglis

  3. Department of Chemistry, University of Helsinki, Helsinki, Finland

    Outi M. Keinänen

  4. PhD Program in Chemistry, Graduate Center of the City University of New York, New York, NY, USA

    Brian M. Zeglis

  5. PhD Program in Biochemistry, Graduate Center of the City University of New York, New York, NY, USA

    Brian M. Zeglis

  6. Department of Radiology, Weill Cornell Medicine, New York, NY, USA

    Brian M. Zeglis

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Correspondence to Brian M. Zeglis .

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Editors and Affiliations

  1. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Lisa Bodei

  2. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Jason S. Lewis

  3. Hunter College - CUNY, New York, NY, USA

    Brian M. Zeglis

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Keinänen, O.M., Zeglis, B.M. (2023). Pretargeted Radiopharmaceutical Therapy. In: Bodei, L., Lewis, J.S., Zeglis, B.M. (eds) Radiopharmaceutical Therapy. Springer, Cham. https://doi.org/10.1007/978-3-031-39005-0_21

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