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Review
. 2023 Jul 19;24(14):11626.
doi: 10.3390/ijms241411626.

Targeted Alpha-Particle Therapy: A Review of Current Trials

Albert Jang  1 , Ayse T Kendi  2 , Geoffrey B Johnson  2   3 , Thorvardur R Halfdanarson  4 , Oliver Sartor  2   4   5
Affiliations
Review

Targeted Alpha-Particle Therapy: A Review of Current Trials

Albert Jang et al. Int J Mol Sci. .

Abstract

Radiopharmaceuticals are rapidly developing as a field, with the successful use of targeted beta emitters in neuroendocrine tumors and prostate cancer serving as catalysts. Targeted alpha emitters are in current development for several potential oncologic indications. Herein, we review the three most prevalently studied conjugated/chelated alpha emitters (225actinium, 212lead, and 211astatine) and focus on contemporary clinical trials in an effort to more fully appreciate the breadth of the current evaluation. Phase I trials targeting multiple diseases are now underway, and at least one phase III trial (in selected neuroendocrine cancers) is currently in the initial stages of recruitment. Combination trials are now also emerging as alpha emitters are integrated with other therapies in an effort to create solutions for those with advanced cancers. Despite the promise of targeted alpha therapies, many challenges remain. These challenges include the development of reliable supply chains, the need for a better understanding of the relationships between administered dose and absorbed dose in both tissue and tumor and how that predicts outcomes, and the incomplete understanding of potential long-term deleterious effects of the alpha emitters. Progress on multiple fronts is necessary to bring the potential of targeted alpha therapies into the clinic.

Keywords: actinium-225; astatine-211; lead-212; radiopharmaceuticals; targeted alpha therapy.

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Conflict of interest statement

A.T.K. has served as a consultant for Novartis and has received research support from Novartis. Mayo Clinic receives funding from Novartis, Pfizer, MedTrace, Clarity, Clovis, and ViewPoint/Perspective for research conducted by G.B.J. Mayo Clinic also receives funding for consultations conducted by G.B.J with Pfizer, Novartis, Curium, Blue Earth, AstraZeneca and Lantheus. Companies founded by G.B.J. include Nucleus RadioPharma and The Green Clinic. Mayo Clinic and G.B.J. hold pending patents on radionuclide theragnostic technologies. T.R.H. has served as a consultant for Ipsen, TerSera, Advanced Accelerator Applications, Isotopen Technologien Muenchen, Crinetics, Viewpoint Molecular Targeting, and Camurus and has received research support from Thermo Fisher Scientific, Advanced Accelerator Applications, Camurus, Crinetics, and Isotopen Technologien Muenchen. O.S. has served as a consultant for Advanced Accelerator Applications (AAA), Astellas, AstraZeneca, Bayer, Blue Earth Diagnostics, Inc., Bavarian Nordic, Bristol Myers Squibb, Clarity Pharmaceuticals, Clovis, Constellation, Dendreon, EMD Serono, Fusion, Isotopen Technologien Meunchen, Janssen, Myovant, Myriad, Noria Therapeutics, Inc., Novartis, Noxopharm, Progenics, POINT Biopharma, Pfizer, Sanofi, Tenebio, Telix, and Theragnostics, has received grant/research support from Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, Constellation, Endocyte, Invitae, Janssen, Lantheus, Merck, Progenics, and Tenebio, and has equity in Ratio, Convergent, Telix, Fusion, and POINT Biopharma. A.J. declares no conflict of interest.

References

    1. Parker C., Nilsson S., Heinrich D., Helle S.I., O’Sullivan J.M., Fosså S.D., Chodacki A., Wiechno P., Logue J., Seke M., et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N. Engl. J. Med. 2013;369:213–223. doi: 10.1056/NEJMoa1213755. - DOI - PubMed
    1. Guerra Liberal F.D.C., O’Sullivan J.M., McMahon S.J., Prise K.M. Targeted Alpha Therapy: Current Clinical Applications. Cancer Biother. Radiopharm. 2020;35:404–417. doi: 10.1089/cbr.2020.3576. - DOI - PubMed
    1. Nelson B.J.B., Andersson J.D., Wuest F. Targeted Alpha Therapy: Progress in Radionuclide Production, Radiochemistry, and Applications. Pharmaceutics. 2020;13:49. doi: 10.3390/pharmaceutics13010049. - DOI - PMC - PubMed
    1. Eychenne R., Chérel M., Haddad F., Guérard F., Gestin J.F. Overview of the Most Promising Radionuclides for Targeted Alpha Therapy: The “Hopeful Eight”. Pharmaceutics. 2021;13:906. doi: 10.3390/pharmaceutics13060906. - DOI - PMC - PubMed
    1. Miederer M., Scheinberg D.A., McDevitt M.R. Realizing the potential of the Actinium-225 radionuclide generator in targeted alpha particle therapy applications. Adv. Drug Deliv. Rev. 2008;60:1371–1382. doi: 10.1016/j.addr.2008.04.009. - DOI - PMC - PubMed

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