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Title: 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:
 [1];  [2];  [3];  [3];  [3];  [1];  [3];  [4];  [3];  [2];  [1]
  1. Univ. of New Mexico, Albuquerque, NM (United States). Radiopharmaceutical Sciences Program. College of Pharmacy. Health Sciences Center
  2. Univ. of New Mexico Comprehensive Cancer Center, Albuquerque, NM (United States). Experimental Therapeutics Unit
  3. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  4. 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 Lab. (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:
Journal Article: 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. 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, and Norenberg, Jeffrey P. Thu . "Alpha-Emitters and Targeted Alpha Therapy in Oncology: from Basic Science to Clinical Investigations". United States. doi: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},
issn = {1776-2596},
number = 2,
volume = 13,
place = {United States},
year = {2018},
month = {2}
}

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Free Publicly Available Full Text
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Cited by: 8 works
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Figures / Tables:

Fig. 1 Fig. 1 : Path length and ionization density of $α$-particles versus $β$-particles

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Works referenced in this record:

Preclinical Evaluation of the α-Particle Generator Nuclide 225Ac for Somatostatin Receptor Radiotherapy of Neuroendocrine Tumors
journal, June 2008


Targeted α-particle radiotherapy with 211At-labeled monoclonal antibodies
journal, October 2007


An 225Ac/213Bi generator system for therapeutic clinical applications: construction and operation
journal, May 1999

  • McDevitt, Michael R.; Finn, Ronald D.; Sgouros, George
  • Applied Radiation and Isotopes, Vol. 50, Issue 5, p. 895-904
  • DOI: 10.1016/S0969-8043(98)00151-1

    Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.