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Radiotheranostics in oncology: current challenges and emerging opportunities

Abstract

Structural imaging remains an essential component of diagnosis, staging and response assessment in patients with cancer; however, as clinicians increasingly seek to noninvasively investigate tumour phenotypes and evaluate functional and molecular responses to therapy, theranostics — the combination of diagnostic imaging with targeted therapy — is becoming more widely implemented. The field of radiotheranostics, which is the focus of this Review, combines molecular imaging (primarily PET and SPECT) with targeted radionuclide therapy, which involves the use of small molecules, peptides and/or antibodies as carriers for therapeutic radionuclides, typically those emitting α-, β- or auger-radiation. The exponential, global expansion of radiotheranostics in oncology stems from its potential to target and eliminate tumour cells with minimal adverse effects, owing to a mechanism of action that differs distinctly from that of most other systemic therapies. Currently, an enormous opportunity exists to expand the number of patients who can benefit from this technology, to address the urgent needs of many thousands of patients across the world. In this Review, we describe the clinical experience with established radiotheranostics as well as novel areas of research and various barriers to progress.

Key points

  • Radiotheranostics combines molecular imaging (primarily PET and SPECT) with targeted radionuclide therapy, typically with radionuclides that emit α-, β- or auger-radiation.

  • The exponential, global expansion of radiotheranostics in oncology stems from the potential to target and eliminate tumour cells with minimal adverse effects owing to a mechanism of action that is distinctly different from that of most other systemic therapies.

  • Approvals of new radiotheranostic agents such as 177Lu-DOTATATE and 177Lu-PSMA-617 alongside the availability of companion diagnostic agents (such as 68Ga-DOTATATE and 68Ga-PSMA-11, respectively) have driven a resurgence of interest in the field that is driving numerous clinical trials testing novel radiotheranostics.

  • Novel and potentially clinically important radiotheranostic approaches are expanding the range of targets to include those present in the tumour microenvironment, such as blood vessels, cancer-associated fibroblasts, the stromal matrix and immune cells.

  • Although access to radiotheranostics is expanding, challenges such as lack of isotope availability, shortages of trained personnel, regulatory burdens and costs might all limit the extent of global dissemination.

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Fig. 1: Overview of the concept of radiotheranostics.
Fig. 2: Responses to approved theranostics, as demonstrated using their imaging counterpart.
Fig. 3: The predicted global nuclear medicine market 2013–2026.
Fig. 4: Therapeutic approaches involving radiotheranostics.

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Acknowledgements

The authors thank G. Scott for the careful editing of this manuscript and S. Lapi (University of Alabama) and J. Engle (University of Wisconsin-Madison) for help with Table 1. This work was supported in part by NIH grants R35 CA232130 (J.S.L.) and P30 CA008748 (J.S.L., L.B., H.S.), and NHMRC Investigator grant 1177837 (A.M.S.).

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L.B. has acted as a consultant and/or speaker for AAA-Novartis, Clovis Oncology, Iba, ITM and MTTI and received research funding from AAA-Novartis. K.H. has received personal fees from Adacap, Aktis Oncology, Amgen, Bayer, BTG, Curium, Endocyte, GE Healthcare, IPSEN, Pharma15, Novartis, Siemens Healthineers, SIRTEX, Theragnostics and YMabs; has received non-financial support from ABX and Sofie Biosciences and has received research funding from BTG. A.M.S. has acted as a consultant of Imagion Bio and ImmunOs; has received research funding from AbbVie, AVID, Cyclotek, Curis; has recevied research funding from AVID, Adalta, EMD Serono, Fusion, Humanigen, ITM, Merck, Medimmune, Telix Pharmaceuticals and Theramyc, and is a co-founder of Certis Therapeutics and Paracrine Therapeutics. J.S.L. has acted as an adviser of Boxer, Clarity Pharmaceuticals, Curie Therapeutics, Earli, Evergreen Theragnostics, Telix Pharmaceuticals, TPG Capital and Varian Medical Systems; is a co-inventor on technologies licensed to Diaprost, Daiichi Sankyo, Elucida Oncology, Macrocyclics and Samus Therapeutics; and is the co-founder of, and holds equity in, pHLIP and Sharp RTx. H.S. declares no competing interests.

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Bodei, L., Herrmann, K., Schöder, H. et al. Radiotheranostics in oncology: current challenges and emerging opportunities. Nat Rev Clin Oncol 19, 534–550 (2022). https://doi.org/10.1038/s41571-022-00652-y

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