Tumor therapy with targeted atomic nanogenerators.
Abstract
A single, high linear energy transfer alpha particle can kill a target cell. We have developed methods to target molecular-sized generators of alpha-emitting isotope cascades to the inside of cancer cells using actinium-225 coupled to internalizing monoclonal antibodies. In vitro, these constructs specifically killed leukemia, lymphoma, breast, ovarian, neuroblastoma, and prostate cancer cells at becquerel (picocurie) levels. Injection of single doses of the constructs at kilobecquerel (nanocurie) levels into mice bearing solid prostate carcinoma or disseminated human lymphoma induced tumor regression and prolonged survival, without toxicity, in a substantial fraction of animals. Nanogenerators targeting a wide variety of cancers may be possible.
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225Ac is classified as a nanogenerator or in vivo generator.
“As such, 225Ac is classified as nanogenerator or in vivo generator (77).”
From Alpha-peptide receptor radionuclide therapy using actinium-225 labeled somatostatin receptor agonists and antagonists (2022) · cites this paper as [77]
Chelation of 225Ac is a slow reaction demanding extensive heating and a high amount of ligand for an adequate yield.
“Moreover, chelation of 225Ac is a slow reaction demanding extensive heating and high amount of ligand for an adequate yield (77, 116, 117).”
From Alpha-peptide receptor radionuclide therapy using actinium-225 labeled somatostatin receptor agonists and antagonists (2022) · cites this paper as [77]
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- Authors
- McDevitt, M. R., Ma, D., Lai, L. T., Simon, J., Borchardt, P., Frank, R. K., Wu, K., Pellegrini, V., Curcio, M. J., Miederer, M., Bander, N. H., & Scheinberg, D. A.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- The Dow Chemical Company, Freeport, TX 77541, USA.
- NewYork–Presbyterian Hospital (US)
- Venue
- Science
- Published
- 2001-11-16
- Volume
- 294
- Issue
- 5546
- Pages
- 1537-1540
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2171140185
- Cited by
- 501
- References
- 18
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 16 · 2023: 19 · 2022: 26 · 2021: 18 · 2020: 26 · 2019: 20 · 2018: 24 · 2017: 20 · 2016: 17 · 2015: 8 · 2014: 17 · 2013: 17 · 2012: 12
- FWCI
- 22.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (P01 33049)
- National Cancer Institute (R01CA055349, R01-CA 55349)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Physical Sciences › Energy › Nuclear Energy and Engineering › Advanced Energy Technologies and Civil Engineering Innovations
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- actinium-225, targeted alpha therapy, tumor cell killing, prostate cancer, lymphoma, tumor regression, radioimmunotherapy
- MeSH terms
- Actinium, Alpha Particles, Animals, Antibodies, Monoclonal, Female, Half-Life, Heterocyclic Compounds, 1-Ring, Humans, Lymphoma, Male, Mice, Nude, Neoplasm Transplantation, Neoplasms, Prostatic Neoplasms, Tumor Cells, Cultured, Survival Rate, Radioimmunotherapy, Prostate-Specific Antigen, Linear Energy Transfer, Immunoconjugates, Mice
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