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Advances in Radioligand Theranostics in Oncology

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Abstract

Theranostics with radioligands (radiotheranostics) has played a pivotal role in oncology. Radiotheranostics explores the molecular targets expressed on tumor cells to target them for imaging and therapy. In this way, radiotheranostics entails non-invasive demonstration of the in vivo expression of a molecular target of interest through imaging followed by the administration of therapeutic radioligand targeting the tumor-expressed molecular target. Therefore, radiotheranostics ensures that only patients with a high likelihood of response are treated with a particular radiotheranostic agent, ensuring the delivery of personalized care to cancer patients. Within the last decades, a couple of radiotheranostics agents, including Lutetium-177 DOTATATE (177Lu-DOTATATE) and Lutetium-177 prostate-specific membrane antigen (177Lu-PSMA), were shown to prolong the survival of cancer patients compared to the current standard of care leading to the regulatory approval of these agents for routine use in oncology care. This recent string of successful approvals has broadened the interest in the development of different radiotheranostic agents and their investigation for clinical translation. In this work, we present an updated appraisal of the literature, reviewing the recent advances in the use of established radiotheranostic agents such as radioiodine for differentiated thyroid carcinoma and Iodine-131-labeled meta-iodobenzylguanidine therapy of tumors of the sympathoadrenal axis as well as the recently approved 177Lu-DOTATATE and 177Lu-PSMA for differentiated neuroendocrine tumors and advanced prostate cancer, respectively. We also discuss the radiotheranostic agents that have been comprehensively characterized in preclinical studies and have shown some clinical evidence supporting their safety and efficacy, especially those targeting fibroblast activation protein (FAP) and chemokine receptor 4 (CXCR4) and those still being investigated in preclinical studies such as those targeting poly (ADP-ribose) polymerase (PARP) and epidermal growth factor receptor 2.

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Authors and Affiliations

  1. Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, NE, Atlanta, GA, 30322, USA

    Ismaheel O. Lawal

  2. Department of Nuclear Medicine, University of Pretoria, Pretoria, 0001, South Africa

    Ismaheel O. Lawal, Honest Ndlovu, Kgomotso M. G. Mokoala, Stuart S. More & Mike M. Sathekge

  3. Department of Radiology and Nuclear Medicine, Sultan Qaboos Comprehensive Cancer Care and Research Center, Muscat, Oman

    Sofiullah O. Abubakar

  4. Nuclear Medicine Research Infrastructure (NuMeRI), Steve Biko Academic Hospital, Pretoria, 0001, South Africa

    Honest Ndlovu, Kgomotso M. G. Mokoala & Mike M. Sathekge

  5. Division of Nuclear Medicine, Department of Radiation Medicine, University of Cape Town, Cape Town, 7700, South Africa

    Stuart S. More

Authors
  1. Ismaheel O. Lawal
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  2. Sofiullah O. Abubakar
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  3. Honest Ndlovu
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  4. Kgomotso M. G. Mokoala
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  6. Mike M. Sathekge
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Correspondence to Ismaheel O. Lawal.

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I.O.L, S.O.A., H.N., K.M.G.M., S.S.M., and M.M.S. have no competing interests to declare that are relevant to the content of this article.

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Literature review: I.O.L. and S.O.A. Initial draft of manuscript: I.O.L. and S.O.A. Critical review and editing of manuscript: I.O.L., S.O.A., H.N., K.M.G.M., S.S.M., and M.M.S.

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Lawal, I.O., Abubakar, S.O., Ndlovu, H. et al. Advances in Radioligand Theranostics in Oncology. Mol Diagn Ther (2024). https://doi.org/10.1007/s40291-024-00702-4

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