Abstract
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.
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Abbreviations
- 2B–DOTA-NCS:
-
2-(p-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaceticacid
- AIC:
-
Alpha Immunoconjugate
- BNL:
-
Brookhaven National Laboratory
- BLIP:
-
Brookhaven Linac Isotope Producer
- C-DEPA:
-
1, 7-[2-(bis-carboxymethyl-amino)-ethyl]-4,10-biscarboxymethyl-1,4,7,10-tetraaza-cyclododec-1-yl-acetic acid
- CHX-A-DTPA:
-
cyclohexyl diethylenetriaminepentaacetic acid
- DMP:
-
2,3-Dimercapto-1-propanesulfonic acid
- DMSA:
-
Dimercaptosuccinic acid
- DOTA:
-
1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaceticacid
- DOTA-SCN:
-
4-isothiocyanate-benzyl 1,4,7,10-tetraazacyclododecane-N′, N″, N″’,N″” tetraacetic acid
- DOTATOC:
-
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
- DOTMP:
-
1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonic
- DOTPA:
-
1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrapropionic acid
- DTPA:
-
diethylenetriaminepentaaceticacid
- EDTA:
-
2-({2-[Bis(carboxymethyl)amino]ethyl}(carboxymethyl)amino)acetic acid
- FcRn:
-
Neonatal Fc Receptors
- HEHA-NCS:
-
2-(4-isothiocyanatobenzyl)-1,4,7,10,13, 16-hexaazacyclohexadecane- 1,4,7,10,13,16hexaacetic acid
- HPLC:
-
High Pressure Liquid Chromatography
- IAEA:
-
International Atomic Energy Association
- IPF:
-
Isotope Production Facility
- LANL:
-
Los Alamos National Laboratory
- LANSCE:
-
Los Alamos National Laboratory Neutron Sciences Center
- LET:
-
Linear Energy Transfer
- MeO-DOTA-NCS:
-
a-(5-isothiocyanato-2-methoxyphenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaceticacid
- MIA:
-
Melanoma Inhibitory-Activity
- MIRD:
-
Medical Internal Radiation Dosimetry
- NSACI:
-
Nuclear Science Advisory Committee
- ORNL:
-
Oak Ridge National Laboratories
- PEPA:
-
1,4,7,10,13-pentaazacyclpentadecane-N, N, N, N, N pentaacetic acid
- PRRT:
-
Peptide Receptor Radiation Therapy
- RBE:
-
Relative Biological Effectiveness
- RIT:
-
Radio Immuno Therapy
- TAT:
-
Targeted Alpha Therapy
- TCMC:
-
2-(4-isothiocyanotobenzyl)-1, 4, 7, 10-tetraaza-1, 4, 7, 10-tetra-(2-carbamonyl methyl)-cyclododecane
- TETPA:
-
1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrapropionic acid
- TETA:
-
1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid
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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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Makvandi, M., Dupis, E., Engle, J.W. et al. Alpha-Emitters and Targeted Alpha Therapy in Oncology: from Basic Science to Clinical Investigations. Targ Oncol 13, 189–203 (2018). https://doi.org/10.1007/s11523-018-0550-9
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DOI: https://doi.org/10.1007/s11523-018-0550-9