Liposomal encapsulation of alpha particle emittors and uses thereof
AssigneeSloan-Kettering Institute for Cancer Research
InventorsGeorge Sgouros, James L. Thomas, David A. Scheinberg, Michael R. McDevitt, Stavroula Sofou
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Abstract
The present invention provides targeted delivery of alpha particle-emitting radionuclides and their alpha-emitting progeny using liposomal encapsulation to reduce the loss of daughter radionuclides from the targeting vehicle and, therefore, from the tumor site. Also provided are encapsulated alpha particle-emitting radionuclides.
Claims59
A method of reducing the systemic release of radioactive decay intermediates upon administration of an alpha particle-emitting radionuclide to an individual, comprising the steps of:
- incorporating said radionuclide into large liposomes, said liposomes having a diameter sufficient to retain at least a majority of said radioactive decay intermediates;
- and
- administering said large liposomes to said individual, wherein retention within said large liposomes of said radioactive decay intermediates produced by said radionuclide reduces the systemic release thereof.
A method of targeting cells in an individual for liposomal delivery of an alpha particle-emitting radionuclide thereto with reduced systemic release of radioactive decay intermediates comprising the steps of:
- entrapping said radionuclide within small liposomal vesicles;
- incorporating said entrapped radionuclide into the aqueous phase of large liposomes, said liposomes having a diameter sufficient to retain at least a majority of the radioactive decay intermediates of said radionuclide, said liposome comprising:
- polyethyleneglycol-linked lipids (PEG-lipids) on outer membranes thereof;
- and
- a targeting agent attached to the PEG-lipids, said targeting agent specific to the cells;
- and
- delivering said radionuclide to the cells whereby said targeting agents target the cells while retention within said large liposomes of said radioactive decay intermediates produced by said radionuclide reduces the systemic release thereof.
A method of targeting cancer cells expressing HER-2/neu protein in an individual for liposomal delivery of Ac-225 thereto with reduced systemic release of radioactive decay intermediates thereof comprising the steps of:
- entrapping said Ac-225 within small liposomal vesicles;
- incorporating said entrapped Ac-225 into the aqueous phase of large liposomes, said liposomes having a diameter sufficient to retain at least a majority of the radioactive decay intermediates of Ac-225, said liposome comprising:
- polyethyleneglycol-linked lipids (PEG-lipids) incorporated into outer membranes thereof;
- and
- Herceptin antibodies attached to the PEG-lipids;
- and
- delivering said Ac-225 to the cancer cells whereby said Herceptin targets the HER-2/neu protein expressed on the cells while retention within said large liposomes of said radioactive decay intermediates produced by said radionuclide reduces the systemic release thereof.
An encapsulated alpha particle emitting radionuclide, comprising:
- said alpha particle emitting radionuclide;
- small liposome vesicles entrapping said alpha particle emitting radionuclide;
- and
- a large liposome incorporating said small liposome vesicles, said large liposome having a diameter sufficient to retain at least a majority of radioactive decay intermediates, said alpha particle emitting radionuclide thereby encapsulated therein.
Dependencies are inferred from the claim text.