Recent advances and impending challenges for the radiopharmaceutical sciences in oncology

Suzanne E Lapi¹, Peter J H Scott², Andrew M Scott³, Albert D Windhorst⁴, Brian M Zeglis⁵, May Abdel-Wahab⁶, Richard P Baum⁷, John M Buatti⁸, Francesco Giammarile⁹, Ana P Kiess¹⁰, Amirreza Jalilian¹¹, Peter Knoll¹², Aruna Korde¹¹, Jolanta Kunikowska¹³, Sze Ting Lee³, Diana Paez¹⁴, Jean-Luc Urbain¹⁵, Jingjing Zhang¹⁶, Jason S Lewis¹⁷

Affiliations

¹ Departments of Radiology and Chemistry, O'Neal Comprehensive Cancer Center, University of Alabama, Birmingham, AL, USA.
² Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
³ Department of Molecular Imaging and Therapy, Austin Health, Melbourne, VIC, Australia; Olivia Newton-John Cancer Research Institute, Melbourne, VIC, Australia; School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia; Department of Surgery, Faculty of Medicine, University of Melbourne, Melbourne, VIC, Australia.
⁴ Department of Radiology & Nuclear Medicine, Amsterdam UMC, Amsterdam, Netherlands; Cancer Center Amsterdam, Vrije Universiteit, Amsterdam, Netherlands.
⁵ Department of Chemistry, Hunter College, City University of New York, New York City, NY, USA; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York City, NY, USA; Department of Radiology, Weill Cornell Medical College, New York City, NY, USA.
⁶ Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria.
⁷ Deutsche Klinik für Diagnostik (DKD Helios Klinik) Wiesbaden, Curanosticum MVZ Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, Germany.
⁸ Department of Radiation Oncology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
⁹ Nuclear Medicine and Diagnostic Imaging Section, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria; Centre Leon Bérard, Lyon, France.
¹⁰ Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹ Radiochemistry and Radiotechnology Section, Division of Physical and Chemical Sciences, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria.
¹² Dosimetry and Medical Radiation Physics Section, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria.
¹³ Nuclear Medicine Department, Medical University of Warsaw, Warsaw, Poland.
¹⁴ Nuclear Medicine and Diagnostic Imaging Section, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria.
¹⁵ Department of Radiology-Nuclear Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
¹⁶ Department of Diagnostic Radiology, National University of Singapore, Singapore; Clinical Imaging Research Centre, Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
¹⁷ Department of Radiology, Memorial Sloan Kettering Cancer Center, New York City, NY, USA; Department of Radiology, Weill Cornell Medical College, New York City, NY, USA; Department of Pharmacology, Weill Cornell Medical College, New York City, NY, USA. Electronic address: lewisj2@mskcc.org.

PMID: 38821098
PMCID: PMC11340123
DOI: 10.1016/S1470-2045(24)00030-5

Review

Recent advances and impending challenges for the radiopharmaceutical sciences in oncology

Suzanne E Lapi et al. Lancet Oncol. 2024 Jun.

. 2024 Jun;25(6):e236-e249.

doi: 10.1016/S1470-2045(24)00030-5.

Authors

Affiliations

¹ Departments of Radiology and Chemistry, O'Neal Comprehensive Cancer Center, University of Alabama, Birmingham, AL, USA.
² Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
³ Department of Molecular Imaging and Therapy, Austin Health, Melbourne, VIC, Australia; Olivia Newton-John Cancer Research Institute, Melbourne, VIC, Australia; School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia; Department of Surgery, Faculty of Medicine, University of Melbourne, Melbourne, VIC, Australia.
⁴ Department of Radiology & Nuclear Medicine, Amsterdam UMC, Amsterdam, Netherlands; Cancer Center Amsterdam, Vrije Universiteit, Amsterdam, Netherlands.
⁵ Department of Chemistry, Hunter College, City University of New York, New York City, NY, USA; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York City, NY, USA; Department of Radiology, Weill Cornell Medical College, New York City, NY, USA.
⁶ Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria.
⁷ Deutsche Klinik für Diagnostik (DKD Helios Klinik) Wiesbaden, Curanosticum MVZ Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, Germany.
⁸ Department of Radiation Oncology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
⁹ Nuclear Medicine and Diagnostic Imaging Section, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria; Centre Leon Bérard, Lyon, France.
¹⁰ Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹ Radiochemistry and Radiotechnology Section, Division of Physical and Chemical Sciences, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria.
¹² Dosimetry and Medical Radiation Physics Section, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria.
¹³ Nuclear Medicine Department, Medical University of Warsaw, Warsaw, Poland.
¹⁴ Nuclear Medicine and Diagnostic Imaging Section, Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria.
¹⁵ Department of Radiology-Nuclear Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
¹⁶ Department of Diagnostic Radiology, National University of Singapore, Singapore; Clinical Imaging Research Centre, Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
¹⁷ Department of Radiology, Memorial Sloan Kettering Cancer Center, New York City, NY, USA; Department of Radiology, Weill Cornell Medical College, New York City, NY, USA; Department of Pharmacology, Weill Cornell Medical College, New York City, NY, USA. Electronic address: lewisj2@mskcc.org.

PMID: 38821098
PMCID: PMC11340123
DOI: 10.1016/S1470-2045(24)00030-5

Abstract

This paper is the first of a Series on theranostics that summarises the current landscape of the radiopharmaceutical sciences as they pertain to oncology. In this Series paper, we describe exciting developments in radiochemistry and the production of radionuclides, the development and translation of theranostics, and the application of artificial intelligence to our field. These developments are catalysing growth in the use of radiopharmaceuticals to the benefit of patients worldwide. We also highlight some of the key issues to be addressed in the coming years to realise the full potential of radiopharmaceuticals to treat cancer.

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Conflict of interest statement

Declaration of interests SEL reports research support from Navidea Biopharmaceuticals, Fusion Pharmaceuticals, Cytosite Biopharma, Viewpoint Molecular Targeting, and Genzyme Corporation; has acted as an advisor for NorthStar Medical Radioisotopes and Trevarx Biomedical; and is supported by the Department of Energy as part of the Department of Energy University Isotope Network under grant DESC0021269. PJHS reports research support from Bristol Myers Squibb, Telix Pharmaceuticals, and Radionetics Oncology; has acted as an adviser to Synfast Consulting and Telix Pharmaceuticals; holds equity in Bristol Myers Squibb, Telix Pharmaceuticals, and Novartis; and is supported by National Institutes of Health R01 EB021155. AMS reports trial funding from EMD Serono, ITM, Telix Pharmaceuticals, AVID Radiopharmaceuticals, Fusion Pharmaceuticals, and Cyclotek; research funding from Medimmune, AVID Radiopharmaceuticals, Adalta, Antengene, Humanigen, Telix Pharmaceuticals, and Theramyc; is on the advisory boards of Imagion and ImmunOs; and is supported by Australian National Health and Medical Research Council grant number 1177837. ADW reports his role as the Editor in Chief of Nuclear Medicine and Biology. BMZ holds equity in Summit Biomedical Imaging. RPB is an advisor to 3B Pharmaceuticals (Berlin, Germany), ITM, Full Life Technologies, Sinotau, Jiangsu Huayi Technology, and Telix Pharmaceuticals. APK reports clinical trial funding from Novartis, Bayer, POINT, and Merck; and unpaid consulting for Novartis. JK reports an unrestricted grant from Janssen, and consulting fees from Telix and Novartis. JSL reports research support from Clarity Pharmaceuticals and Avid Radiopharmaceuticals; has acted as an adviser of Alpha-9 Theranostics, Clarity Pharmaceuticals, Earli, Evergreen Theragnostics, Inhibrix, Precirix, and Telix Pharmaceuticals; is a co-inventor on technologies licensed to Diaprost, Elucida Oncology, Theragnostics, CheMatech, Clarity Pharmaceuticals, and Samus Therapeutics; is the co-founder of pHLIP; holds equity in Summit Biomedical Imaging, Telix Pharmaceuticals, Clarity Pharmaceuticals, and Evergreen Theragnostics; and is supported by National Institutes of Health R35 CA232130. All other authors declare no competing interests.

Figures

**FIGURE 1:**
Illustration of how radiotheranostics are used: imaging scans acquired using a tumour-targeting vector (green hexagon) labelled with a diagnostic radionuclide (yellow) facilitate patient selection, individualized dosimetry, and treatment monitoring for radiopharmaceutical therapy using the same vector labelled with a therapeutic radionuclide (orange).

**Figure 2A:**
[¹⁸F]FDG-PET scans of a 60-year-old male diagnosed in April 2014 with pancreatic NEN (Ki67 52%) who underwent Whipple surgery, CAPTEM chemo, liver resection, and 4 cycles Lutathera in 2020. Upon recurrence in late 2021, further disease progression was observed despite numerous other treatments. Nearly complete hepatic remission was observed after PRRT with [¹⁷⁷Lu]Lu-DOTA-LM3 (timing of doses shown with blue arrows) and has persisted for 2 years^. **Figure 2B:** [¹⁸F]FDG-PET scans of a 53-year-old patient diagnosed in 2010 with ovarian adenocarcinoma G3 who underwent surgery and chemotherapy. After recurrence in 2021, progressive disease was observed despite various chemo- and immunotherapies. Complete remission was achieved after tandem [¹⁷⁷Lu]Lu/[²²⁵Ac]Ac-3BP-3940 treatment (timing of doses shown with blue arrows) and is ongoing after 19 months.

See this image and copyright information in PMC

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Recent advances and impending challenges for the radiopharmaceutical sciences in oncology

Affiliations

Recent advances and impending challenges for the radiopharmaceutical sciences in oncology

Authors

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Abstract

Conflict of interest statement

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