Development of Targeted Alpha Particle Therapy for Solid Tumors

Authors

Narges K. Tafreshi, Lee Moffitt Cancer Center & Research Institute
Michael L. Doligalski, Lee Moffitt Cancer Center & Research Institute
Christopher J. Tichacek, Lee Moffitt Cancer Center & Research Institute
Darpan N. Pandya, Wake Forest University Health Sciences
Mikalai M. Budzevich, Lee Moffitt Cancer Center & Research Institute
Ghassan el-Haddad, Lee Moffitt Cancer Center & Research Institute
Nikhil I. Khushalani, Lee Moffitt Cancer Center & Research Institute
Eduardo G. Moros, Lee Moffitt Cancer Center & Research Institute, University of South Florida
Mark L. McLaughlin, West Virginia University
Thaddeus J. Wadas, Wake Forest University Health Sciences
David L. Morse, Lee Moffitt Cancer Center & Research Institute, University of South Florida

Author ORCID Identifier

N/A

https://orcid.org/0000-0003-1920-7485

N/A

N/A

N/A

N/A

N/A

https://orcid.org/0000-0003-1964-2460

N/A

https://orcid.org/0000-0002-9913-0336

https://orcid.org/0000-0002-6006-7528

Document Type

Article

Publication Date

2019

College/Unit

School of Pharmacy

Department/Program/Center

Pharmaceutical Sciences

Abstract

Abstract: Targeted alpha-particle therapy (TAT) aims to selectively deliver radionuclides emitting α-particles (cytotoxic payload) to tumors by chelation to monoclonal antibodies, peptides or small molecules that recognize tumor-associated antigens or cell-surface receptors. Because of the high linear energy transfer (LET) and short range of alpha (α) particles in tissue, cancer cells can be significantly damaged while causing minimal toxicity to surrounding healthy cells. Recent clinical studies have demonstrated the remarkable efficacy of TAT in the treatment of metastatic, castration-resistant prostate cancer. In this comprehensive review, we discuss the current consensus regarding the properties of the α-particle-emitting radionuclides that are potentially relevant for use in the clinic; the TAT-mediated mechanisms responsible for cell death; the different classes of targeting moieties and radiometal chelators available for TAT development; current approaches to calculating radiation dosimetry for TATs; and lead optimization via medicinal chemistry to improve the TAT radiopharmaceutical properties. We have also summarized the use of TATs in pre-clinical and clinical studies to date

Digital Commons Citation

Tafreshi, Narges K.; Doligalski, Michael L.; Tichacek, Christopher J.; Pandya, Darpan N.; Budzevich, Mikalai M.; el-Haddad, Ghassan; Khushalani, Nikhil I.; Moros, Eduardo G.; McLaughlin, Mark L.; Wadas, Thaddeus J.; and Morse, David L., "Development of Targeted Alpha Particle Therapy for Solid Tumors" (2019). Faculty & Staff Scholarship. 1419.
https://researchrepository.wvu.edu/faculty_publications/1419

Source Citation

Tafreshi, N. K., Doligalski, M. L., Tichacek, C. J., Pandya, D. N., Budzevich, M. M., El-Haddad, G., Khushalani, N. I., Moros, E. G., McLaughlin, M. L., Wadas, T. J., & Morse, D. L. (2019). Development of Targeted Alpha Particle Therapy for Solid Tumors. Molecules, 24(23), 4314. https://doi.org/10.3390/molecules24234314

Comments

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).