Cited by 157Radiopharmaceutical Chemistry and ApplicationsRadioactivity and Radon MeasurementsChemical Reactions and Isotopes

Development of targeted alpha particle therapy for solid tumors.

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Tafreshi, Narges K., Doligalski, Michael L., Tichacek, Christopher J., Pandya, Darpan N., Budzevich, Mikalai M., El-Haddad, Ghassan, Khushalani, Nikhil I., Moros, Eduardo G. +3 more·2019·Molecules

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.

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  1. [22]Hall E.J. Giaccia A.J. Radiobiology for the Radiologist Lippincott Williams & Wilkins Philadelphia, PA, USA 2006
  2. [49]Greenwood N.N. Earnshaw A. Chemistry of the Elements 2nd ed. Butterworth-Heinemann Oxford, UK 1997 946 0-08-037941-9
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Authors
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.
Affiliations
  • Moffitt Cancer Center (US)
  • Wake Forest University Health Sciences (US)
  • University of South Florida (US)
  • West Virginia University (US)
Corresponding author
Morse, David L.
Venue
Molecules
Publisher
MDPI AG
Published
2019-11-26
Volume
24
Issue
23
Pages
4314
ISSN
1420-3049 (ISSN-L)
OpenAlex
W2990493095
Cited by
157
References
283
Citations by year
2026: 21 · 2025: 25 · 2024: 24 · 2023: 26 · 2022: 23 · 2021: 30 · 2020: 7 · 2018: 1
FWCI
2.25
Type
journal article
Language
en
Open access
Locations
  • Molecules (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • The Research Repository @ WVU (West Virginia University) (submittedVersion, cc-by)
Funders
  • Melanoma Research Alliance
  • National Institutes of Health
  • National Cancer Institute (P50CA168536)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
  • Health Sciences › Health Professions › Radiological and Ultrasound Technology › Radioactivity and Radon Measurements
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Chemical Reactions and Isotopes
Keywords
alpha-emitting radionuclides, radiopharmaceuticals, linear energy transfer, tumor targeting, radiation dosimetry, castration-resistant prostate cancer, metastatic prostate cancer, cell death mechanisms, solid tumors
MeSH terms
Alpha Particles, Animals, Antibodies, Monoclonal, Humans, Neoplasms, Radioisotopes, Radiometry, Radiopharmaceuticals

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