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Cited by 151Radiopharmaceutical Chemistry and ApplicationsChemical Reactions and IsotopesRadioactivity and Radon Measurements

Targeted α-therapy–past, present, future?

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Brechbiel, Martin W.·2007·Dalton Transactions
DOI 10.1039/b704726fPMC PMC2408446
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Abstract

Monoclonal antibodies have become a viable strategy for the delivery of therapeutic, particle emitting radionuclides specifically to tumor cells to either augment anti-tumor action of the native antibodies or to solely take advantage of their action as targeting vectors. Proper and rational selection of radionuclide and antibody combinations is critical to making radioimmunotherapy (RIT) a standard therapeutic modality due to the fundamental and significant differences in the emission of either alpha- and beta-particles. The alpha-particle has a short path length (50-80 microm) that is characterized by high linear energy transfer (100 keV microm(-1)). Actively targeted alpha-therapy potentially offers a more specific tumor cell killing action with less collateral damage to the surrounding normal tissues than beta-emitters. These properties make targeted alpha-therapy an appropriate therapy to eliminate minimal residual or micrometastatic disease. RIT using alpha-emitters such as (213)Bi, (211)At, (225)Ac, and others has demonstrated significant activity in both in vitro and in vivo model systems. Limited numbers of clinical trials have progressed to demonstrate safety, feasibility, and therapeutic activity of targeted alpha-therapy, despite having to traverse complex obstacles. Further advances may require more potent isotopes, additional sources and more efficient means of isotope production. Refinements in chelation and/or radiolabeling chemistry combined with rational improvements of isotope delivery, targeting vectors, molecular targets, and identification of appropriate clinical applications remain as active areas of research. Ultimately, randomized trials comparing targeted alpha-therapy combined with integration into existing standards of care treatment regimens will determine the clinical utility of this modality.

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  • Due to the range of β particles, emitted β particles traverse several cells (10-1000), an effect termed 'cross-fire effect' that is responsible for possible destruction of multiple cells in the vicinity of the tracer-accumulating cell.

    “Due to the range of the β particles in comparison to the diameter of a cell, the emitted β particles traverse several cells (10–1000) [30]. This effect has been termed “cross-fire effect” and is responsible for the possible destruction of multiple cells in the vicinity of the tracer-accumulating cell [31].”

    From Lutathera®: The First FDA- and EMA-Approved Radiopharmaceutical for Peptide Receptor Radionuclide Therapy (2019) · cites this paper as [30]

  • High linear energy transfer renders higher target cell toxicity originating from a higher probability of DNA double strand breaks compared to beta-particles with low linear energy transfer (0.1-1.0 keV/μm).

    “This high LET renders higher target cell toxicity originating from higher probability of DNA double strand breaks (DSB) compared to β-particles with low LET (0.1–1.0 keV/μm) (61).”

    From Alpha-peptide receptor radionuclide therapy using actinium-225 labeled somatostatin receptor agonists and antagonists (2022) · cites this paper as [61]

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Authors
Brechbiel, M. W.
Affiliations
National Institutes of Health (US)
Corresponding author
Brechbiel, Martin W.
ORCID
Brechbiel, Martin W.
Venue
Dalton Transactions
Publisher
Royal Society of Chemistry (RSC)
Published
2007
Issue
43
Pages
4918
ISSN
  • 1477-9226 (ISSN-L)
  • 1477-9234
DOI
10.1039/b704726f
PMC
PMC2408446
OpenAlex
W1979624352
Cited by
151
References
89
Citations by year
2026: 5 · 2025: 9 · 2024: 8 · 2023: 12 · 2022: 10 · 2021: 14 · 2020: 9 · 2019: 9 · 2018: 12 · 2017: 4 · 2016: 9 · 2015: 6 · 2014: 8 · 2013: 3 · 2012: 7
FWCI
0.78
Type
journal article
Language
en
Open access
Locations
  • Dalton Transactions (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (Z01SC006353)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Chemical Reactions and Isotopes
  • Health Sciences › Health Professions › Radiological and Ultrasound Technology › Radioactivity and Radon Measurements
Keywords
targeted alpha therapy, radioimmunotherapy, monoclonal antibodies, alpha-emitting radionuclides, bismuth-213, astatine-211, actinium-225, linear energy transfer, micrometastatic disease, isotope production, tumor targeting
MeSH terms
Alpha Particles, Antibodies, Monoclonal, Humans, Neoplasms, Radioimmunotherapy

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