Tumor therapy with targeted atomic nanogenerators.
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.
McDevitt
M R
MR
Molecular Pharmacology and Therapeutics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Ma
D
D
Lai
L T
LT
Simon
J
J
Borchardt
P
P
Frank
R K
RK
Wu
K
K
Pellegrini
V
V
Curcio
M J
MJ
Miederer
M
M
Bander
N H
NH
Scheinberg
D A
DA
D000186:Actinium / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000512:Alpha Particles / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006573:Heterocyclic Compounds, 1-Ring; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018499:Linear Energy Transfer; D008223:Lymphoma / Q000532:radiotherapy; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000532:radiotherapy*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000532:radiotherapy; D016499:Radioimmunotherapy / Q000379:methods*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D006573:Heterocyclic Compounds, 1-Ring; D018796:Immunoconjugates; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D017430:Prostate-Specific Antigen; D000186:Actinium