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Radionuclide Therapy and Immunomodulation

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Nuclear Medicine and Immunology

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Abstract

External beam radiation therapy (EBRT) stands as one of the pillars of cancer treatment around the world and has been widely used for decades as a curative and palliative therapy. For most of that time, the prevailing explanation for its antitumor effect has been the induction of complex DNA damage leading to cell death. However, there is now an increasing body of evidence demonstrating that alongside direct tumor cell killing, radiation induces an antitumor immune response that can contribute significantly to its therapeutic efficacy. Targeted radionuclide therapy (TRT) represents a distinct form of radiotherapy, which unlike EBRT provides systemic treatment that does not rely on detailed knowledge of tumor location. It is therefore particularly useful for the treatment of metastatic tumors. Therapeutic radioisotopes can be conjugated to targeting moieties such as small molecules, antibodies, or other ligands enabling specific accumulation within the tumor site following systemic administration. These isotopes then provide protracted, low-dose rate radiation to the tumor as the isotope decays. Given its similarity to EBRT, it is likely that TRT is capable of promoting an antitumor immune response that may contribute to its observed clinical efficacy. However, differences in factors such as dose rate, mode of administration, and treatment duration are likely to influence the immune response differently. Here, we summarize the evidence to date that EBRT promotes antitumor immunity and consider the mechanisms of this effect. Based on this understanding, we discuss the possible role of the immune system in TRT and review the literature to date aimed at elucidating this role.

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Authors and Affiliations

  1. Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK

    Rachel Anderson & Katherine Vallis

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  1. Rachel Anderson
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  2. Katherine Vallis
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  1. Department of Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Sara Harsini

  2. Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA

    Abass Alavi

  3. Research Center for Immunodeficiencies, Tehran University of Medical Sciences, Tehran, Iran

    Nima Rezaei

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Anderson, R., Vallis, K. (2022). Radionuclide Therapy and Immunomodulation. In: Harsini, S., Alavi, A., Rezaei, N. (eds) Nuclear Medicine and Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-81261-4_11

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