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Science 16 November 2001:
Vol. 294. no. 5546, pp. 1537 - 1540
DOI: 10.1126/science.1064126
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Reports

Tumor Therapy with Targeted Atomic Nanogenerators

Michael R. McDevitt,1 Dangshe Ma,1 Lawrence T. Lai,1 Jim Simon,2 Paul Borchardt,1 R. Keith Frank,2 Karen Wu,1 Virginia Pellegrini,1 Michael J. Curcio,1 Matthias Miederer,1 Neil H. Bander,3 David A. Scheinberg1*

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.

1 Molecular Pharmacology and Therapeutics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
2 The Dow Chemical Company, Freeport, TX 77541, USA.
3 Department of Urology, New York Presbyterian Hospital-Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA.
*   To whom correspondence should be addressed. E-mail: d-scheinberg{at}ski.mskcc.org

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