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Major advances in radioligand therapy and cancer care

Radioligands are an innovation driven by our increasing understanding of the molecular biology of cancer and the role of radiation in cancer care. This timeline explores the history and future of radioligand therapy (on the right) alongside other innovations in oncology (on the left).

2022

Approval of radioligand therapy for PSMA-positive mCRPC in the US1

2021

First positive preliminary results from a phase III trial on the use of radioligand therapy for mCRPC2

2018

Approval of radioligand therapy for progressive midgut NETs in the US3

First approval of gene therapy (alters the person’s immune cells (T-cells) to fight cancer, also known as CAR-T therapy)4 5

2017

Approval of radioligand therapy for progressive midgut NETs in the EU6

2013

Approval of bone-directed radiotherapy in mCRPC in the EU7 and US8

First approval of immune checkpoint inhibitor (for malignant melanoma)9

2011
2005

Further studies into radioligand therapy for bone metastases10

2004

First radioimmunotherapy approved for lymphoma in the EU11

2002

First radioimmunotherapy approved for lymphoma in the US12

1990s

Approval of bone-directed radiotherapy for pain in bone metastases in EU countries13 14

First monoclonal antibody immunotherapy treatment approved9

1997
1992

Early trials of radioimmunotherapy for lymphoma15

1980s

Early studies and use of radioligand therapy for NETs16-19

1986

Early trials of bone-directed radiotherapy for bone metastases20

1983

First scans of endocrine-related tumours using targeted radioisotopes21 22

First anti-cancer vaccine against hepatitis B virus (a risk factor for liver cancer)4

1981

First hormone therapy approved that blocks the effect of oestrogen9

1978

First use of chemotherapy after surgery (known as adjuvant chemotherapy)4

1975
1973

First PET scanner developed23

First use of chemotherapy4

1949
1942

Early trials of radioactive strontium to treat metastatic bone cancer24

Discovery of hormone therapy for prostate cancer9

1941

First use of radioiodine to treat thyroid cancer (this was the first example of using a radionuclide for cancer treatment)25

First approach combining surgery and radiation9

1937

First use of radiotherapy to cure cancer4

1903
References
  1. Targeted Oncology. FDA Approves Lu 177 Vipivotide Tetraxetan for Metastatic Castration-Resistant Prostate Cancer. Available from: https://www.targetedonc.com/view/fda-approves-177lu-psma-617-for-metastatic-castration-resistant-prostate-cancer  [Accessed 30/03/2022]
  2. Novartis. Novartis announces positive result of phase III study with radioligand therapy 177Lu-PSMA-617 in patients with advanced prostate cancer. Available from: https://www.novartis.com/news/media-releases/novartis-announces-positive-result-phase-iii-study-radioligand-therapy-177lu-psma-617-patients-advanced-prostate-cancer [Accessed 23/03/2021]
  3. National Cancer Institute. FDA Approves New Treatment for Certain Neuroendocrine Tumors. Available from: https://www.cancer.gov/news-events/cancer-currents-blog/2018/lutathera-fda-gastrointestinal-nets [Accessed 12/04/21]
  4. American Society of Clinical Oncology. Cancer progress timeline. Available from: https://www.asco.org/research-guidelines/cancer-progress-timeline [Accessed 08/09/19]
  5. Whatisbiotechnology.org. Immunotherapy: Timeline of key events. Available from: https://www.whatisbiotechnology.org/index.php/timeline/science/immunotherapy/80 [Accessed 09/09/2019]
  6. European Medicines Agency. Lutathera. [Updated 02/04/19]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/lutathera [Accessed 21/01/20]
  7. European Medicines Agency. Xofigo. [Updated 10/01/20]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/xofigo [Accessed 21/01/20]
  8. ASCO. FDA Approves Xofigo for Castration-Resistant Prostate Cancer. Available from: https://www.asco.org/practice-policy/policy-issues-statements/asco-in-action/fda-approves-xofigo-castration-resistant [Accessed 12/04/21]
  9. National Cancer institute at the National Institutes of Health. Milestones in cancer research and discovery. Available from: https://www.cancer.gov/research/progress/250-years-milestones [Accessed 08/09/2019]
  10. Bander NH, Milowsky MI, Nanus DM, et al. 2005. Phase I trial of 177lutetium-labeled J591, a monoclonal antibody to prostate-specific membrane antigen, in patients with androgen-independent prostate cancer. Journal of Clinical Oncology 23(21): 4591-601
  11. European Medicines Agency. Zevalin ibritumomab tiuxetan. [Updated 09/03/20]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/zevalin [Accessed 07/07/20]
  12. Cancer Network. First Radioimmunotherapy Approved by FDA. Available from: https://www.cancernetwork.com/view/first-radioimmunotherapy-approved-fda [Accessed 06/04/21]
  13. Medicines and Healthcare products Regulatory Agency. 2016. SUMMARY OF PRODUCT CHARACTERISTICS: METASTRON. Available from: https://mhraproductsprod.blob.core.windows.net/docs-20200109/c853ecfb95ca6cdf9cea64e782e4e53689779804 [Accessed 08/01/20]
  14. Haute Autorite de Sante – Medical EaPHAD. 2014. TRANSPARENCY COMMITTEE: Opinion 1 October 2014 METASTRON. Available from: https://www.has-sante.fr/upload/docs/application/pdf/2015-10/metastron_version_anglaise_ct13569.pdf [Accessed 08/12/19]
  15. Grillo-López AJ. 2002. Zevalin: the first radioimmunotherapy approved for the treatment of lymphoma. Expert Rev Anticancer Ther 2(5): 485-93
  16. Levine R, Krenning EP. 2017. Clinical history of the theranostic radionuclide approach to neuroendocrine tumors and other types of cancer: historical review based on an interview of Eric P. Krenning by Rachel Levine. Journal of Nuclear Medicine 58(Supplement 2): 3S-9S
  17. Krenning EP, Bakker WH, Breeman WA, et al. 1989. Localisation of endocrine-related tumours with radioiodinated analogue of somatostatin. Lancet (London, England) 1(8632): 242-4
  18. PRRTinfo.org. 2019. What is PRRT? Available from: http://www.prrtinfo.org/prrt [Accessed 08/09/19]
  19. Krenning EP, Kooij PP, Bakker WH, et al. 1994. Radiotherapy with a radiolabeled somatostatin analogue, [111In-DTPA-D-Phe1]-octreotide. A case history. Annals of the New York Academy of Sciences 733: 496-506
  20. Reddy EK, Robinson RG, Mansfield CM. 1986. Strontium 89 for palliation of bone metastases. Journal of the National Medical Association 78(1): 27-32
  21. Nakajo M, Shapiro B, Copp J, et al. 1983. The normal and abnormal distribution of the adrenomedullary imaging agent m-[I-131]iodobenzylguanidine (I-131 MIBG) in man: evaluation by scintigraphy. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 24(8): 672-82
  22. Francis IR, Glazer GM, Shapiro B, et al. 1983. Complementary roles of CT and 131I-MIBG scintigraphy in diagnosing pheochromocytoma. AJR American journal of roentgenology 141(4): 719-25
  23. US Department of Energy – Molecular Nuclear Medicine Legacy. History of PET and MRI. Available from: https://www.doemedicalsciences.org/historypetmri.shtml [Accessed 08/09/2019]
  24. Pecher C. 1942. Biological investigations with radioactive calcium and strontium; preliminary report on the use of radioactive strontium in the treatment of metastatic bone cancer. Berkeley, Los Angeles, USA: University of California Press
  25. McCready VR. 2017. Radioiodine – the success story of Nuclear Medicine. Eur J Nuclear Med Mol Imaging 44(2): 179-82

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