Journal
SCIENCE
Volume 294, Issue 5546, Pages 1537-1540Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1064126
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Funding
- NCI NIH HHS [R01 CA55349] Funding Source: Medline
- PHS HHS [P01 33049] Funding Source: Medline
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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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