Alpha-Emitters and Targeted Alpha Therapy in Oncology: from Basic Science to Clinical Investigations
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. Finally, this review will cover their therapeutic application as well as summarize the investigations that provide the foundation for further clinical development.
- Authors:
-
- Univ. of New Mexico, Albuquerque, NM (United States). Radiopharmaceutical Sciences Program. College of Pharmacy. Health Sciences Center
- Univ. of New Mexico Comprehensive Cancer Center, Albuquerque, NM (United States). Experimental Therapeutics Unit
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Univ. of New Mexico, Albuquerque, NM (United States). Radiopharmaceutical Sciences Program. College of Pharmacy. Health Sciences Center; Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States); Univ. of New Mexico, Albuquerque, NM (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1459839
- Report Number(s):
- LA-UR-16-27976
Journal ID: ISSN 1776-2596
- Grant/Contract Number:
- AC52-06NA25396
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Targeted Oncology
- Additional Journal Information:
- Journal Volume: 13; Journal Issue: 2; Journal ID: ISSN 1776-2596
- Publisher:
- Springer
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 62 RADIOLOGY AND NUCLEAR MEDICINE
Citation Formats
Makvandi, Mehran, Dupis, Edouard, Engle, Jonathan W., Nortier, F. Meiring, Fassbender, Michael E., Simon, Sam, Birnbaum, Eva R., Atcher, Robert W., John, Kevin D., Rixe, Olivier, and Norenberg, Jeffrey P.. Alpha-Emitters and Targeted Alpha Therapy in Oncology: from Basic Science to Clinical Investigations. United States: N. p., 2018.
Web. doi:10.1007/s11523-018-0550-9.
Makvandi, Mehran, Dupis, Edouard, Engle, Jonathan W., Nortier, F. Meiring, Fassbender, Michael E., Simon, Sam, Birnbaum, Eva R., Atcher, Robert W., John, Kevin D., Rixe, Olivier, & Norenberg, Jeffrey P.. Alpha-Emitters and Targeted Alpha Therapy in Oncology: from Basic Science to Clinical Investigations. United States. https://doi.org/10.1007/s11523-018-0550-9
Makvandi, Mehran, Dupis, Edouard, Engle, Jonathan W., Nortier, F. Meiring, Fassbender, Michael E., Simon, Sam, Birnbaum, Eva R., Atcher, Robert W., John, Kevin D., Rixe, Olivier, and Norenberg, Jeffrey P.. Thu .
"Alpha-Emitters and Targeted Alpha Therapy in Oncology: from Basic Science to Clinical Investigations". United States. https://doi.org/10.1007/s11523-018-0550-9. https://www.osti.gov/servlets/purl/1459839.
@article{osti_1459839,
title = {Alpha-Emitters and Targeted Alpha Therapy in Oncology: from Basic Science to Clinical Investigations},
author = {Makvandi, Mehran and Dupis, Edouard and Engle, Jonathan W. and Nortier, F. Meiring and Fassbender, Michael E. and Simon, Sam and Birnbaum, Eva R. and Atcher, Robert W. and John, Kevin D. and Rixe, Olivier and Norenberg, Jeffrey P.},
abstractNote = {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. Finally, this review will cover their therapeutic application as well as summarize the investigations that provide the foundation for further clinical development.},
doi = {10.1007/s11523-018-0550-9},
journal = {Targeted Oncology},
number = 2,
volume = 13,
place = {United States},
year = {2018},
month = {2}
}
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Fig. 1 : Path length and ionization density of $α$-particles versus $β$-particles
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