Targeted Oncology

, Volume 13, Issue 2, pp 189–203 | Cite as

Alpha-Emitters and Targeted Alpha Therapy in Oncology: from Basic Science to Clinical Investigations

  • Mehran Makvandi
  • Edouard Dupis
  • Jonathan W. Engle
  • F. Meiring Nortier
  • Michael E. Fassbender
  • Sam Simon
  • Eva R. Birnbaum
  • Robert W. Atcher
  • Kevin D. John
  • Olivier Rixe
  • Jeffrey P. Norenberg
Review Article


Alpha-emitters are radionuclides that decay through the emission of high linear energy transfer α-particles and possess favorable pharmacologic profiles for cancer treatment. When coupled with monoclonal antibodies, peptides, small molecules, or nanoparticles, the excellent cytotoxic capability of α-particle emissions has generated a strong interest in exploring targeted α-therapy in the pre-clinical setting and more recently in clinical trials in oncology. Multiple obstacles have been overcome by researchers and clinicians to accelerate the development of targeted α-therapies, especially with the recent improvement in isotope production and purification, but also with the development of innovative strategies for optimized targeting. Numerous studies have demonstrated the in vitro and in vivo efficacy of the targeted α-therapy. Radium-223 (223Ra) dichloride (Xofigo®) is the first α-emitter to have received FDA approval for the treatment of prostate cancer with metastatic bone lesions. There is a significant increase in the number of clinical trials in oncology using several radionuclides such as Actinium-225 (225Ac), Bismuth-213 (213Bi), Lead-212 (212Pb), Astatine (211At) or Radium-223 (223Ra) assessing their safety and preliminary activity. This review will cover their therapeutic application as well as summarize the investigations that provide the foundation for further clinical development.





Alpha Immunoconjugate


Brookhaven National Laboratory


Brookhaven Linac Isotope Producer


1, 7-[2-(bis-carboxymethyl-amino)-ethyl]-4,10-biscarboxymethyl-1,4,7,10-tetraaza-cyclododec-1-yl-acetic acid


cyclohexyl diethylenetriaminepentaacetic acid


2,3-Dimercapto-1-propanesulfonic acid


Dimercaptosuccinic acid




4-isothiocyanate-benzyl 1,4,7,10-tetraazacyclododecane-N′, N″, N″’,N″” tetraacetic acid


2-[4-[2-[[(2R)-1-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-4-[[(2R,3R)-1,3-dihydroxybutan-2-yl]carbamoyl]-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicos-19-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]-7,10-bis(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid




1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrapropionic acid




2-({2-[Bis(carboxymethyl)amino]ethyl}(carboxymethyl)amino)acetic acid


Neonatal Fc Receptors


2-(4-isothiocyanatobenzyl)-1,4,7,10,13, 16-hexaazacyclohexadecane- 1,4,7,10,13,16hexaacetic acid


High Pressure Liquid Chromatography


International Atomic Energy Association


Isotope Production Facility


Los Alamos National Laboratory


Los Alamos National Laboratory Neutron Sciences Center


Linear Energy Transfer




Melanoma Inhibitory-Activity


Medical Internal Radiation Dosimetry


Nuclear Science Advisory Committee


Oak Ridge National Laboratories


1,4,7,10,13-pentaazacyclpentadecane-N, N, N, N, N pentaacetic acid


Peptide Receptor Radiation Therapy


Relative Biological Effectiveness


Radio Immuno Therapy


Targeted Alpha Therapy


2-(4-isothiocyanotobenzyl)-1, 4, 7, 10-tetraaza-1, 4, 7, 10-tetra-(2-carbamonyl methyl)-cyclododecane


1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrapropionic acid


1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid


Compliance with Ethical Standards



Conflict of Interest

Olivier Rixe has received honorarium as a member of a scientific committee from Areva Med. All other authors declare no conflict of interest.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Mehran Makvandi
    • 1
  • Edouard Dupis
    • 2
  • Jonathan W. Engle
    • 3
  • F. Meiring Nortier
    • 3
  • Michael E. Fassbender
    • 3
  • Sam Simon
    • 1
  • Eva R. Birnbaum
    • 3
  • Robert W. Atcher
    • 1
    • 3
  • Kevin D. John
    • 3
  • Olivier Rixe
    • 2
  • Jeffrey P. Norenberg
    • 1
  1. 1.Radiopharmaceutical Sciences Program, College of Pharmacy, Health Sciences CenterUniversity of New MexicoAlbuquerqueUSA
  2. 2.Experimental Therapeutics UnitUniversity of New Mexico Comprehensive Cancer CenterAlbuquerqueUSA
  3. 3.Los Alamos National LaboratoryLos AlamosUSA

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