High dose radionuclide complexes for bone marrow suppression

A therapeutic method to increase the efficacy of a chemotherapeutic treatment for a bone-associated pathology in a mammal comprising administering to the mammal, a chemotherapeutic agent and an amount of a complex comprising a radionuclide and a bone targeting ligand sufficient to deliver about 20 to about 60 Gy to the bone marrow of the mammal;

• wherein the efficacy of the chemotherapeutic treatment is increased without a substantial increase in at least one side effect, and wherein the mammal is not subjected to TBI in conjunction with the chemotherapeutic treatment.

A method of treating a bone-associated cancer or non-cancerous disorder of bone marrow comprising administering to a human subject afflicted with said cancer or disorder an effective amount of a macrocyclic aminophosphonate 166Ho complex in combination with an effective high dosage amount of a chemotherapeutic agent, wherein said amounts are effective to suppress the cancer cells or bone marrow cells of said mammal, and wherein said treatment does not substantially increase a side effect associated with the treatment with said chemotherapeutic agent used alone.

A method for treating bone-associated cancer, wherein said method comprises administering to a human in need of such treatment an effective bone marrow suppressing dosage of 166Ho-1,4,7,10-tetraazacyclododecane-tetramethylene-phosphonic acid (DOTMP) complex wherein the ratio of DOTMP to 166Ho is above about 3;

• wherein said dosage delivers from about 20-60 Gy to the bone marrow of said human.

A method for treating infectious diseases in or near bone wherein said method comprises administering to a mammal in need of such treatment a dosage of a radionuclide complexed with a bone targeting ligand, or a physiologically acceptable salt thereof;

• wherein from about 250 to about 3000 megabecquerels per kilogram of body weight of the radionuclide is administered.

A method for treating noncancerous diseases in or near bone wherein said method comprises administering to a mammal in need of such treatment a dosage of a radionuclide complexed with a bone targeting ligand, or a physiologically acceptable salt thereof;

• wherein from about 250 to about 3000 megabecquerels per kilogram of body weight of the radionuclide is administered, without use of TBI.

A method for suppressing bone marrow or treating a bone marrow-associated pathology comprising administering an aqueous pharmaceutical composition to a human in need of such suppression or treatment, wherein said composition comprises an effective amount of a complex of 166Ho with 1,4,7,10-tetraazacyclododecane-tetramethylenephosphonic acid (DOTMP), wherein the mole ratio of DOTMP to 166Ho is above 3, and an effective stabilizing amount of a radioprotectant, so that the composition is stable for at least about 72 hours under ambient conditions.

A liquid pharmaceutical composition comprising 166Ho complexed with 1,4,7,10-tetraazacyclododecanetetramethylene-phosphonic acid (DOTMP) in a mole ratio of DOTMP to 166Ho above 3, and an effective antiradiolytic amount of a pharmaceutically acceptable radioprotectant.

A method for treating a patient afflicted with a hematopoietic genetic defect wherein said method comprises administering to a mammal in need of such treatment a bone marrow suppressing dosage of a radionuclide complexed with a bone targeting ligand, or a physiologically acceptable salt thereof;

• wherein from about 250 to about 3000 megabecquerels per kilogram of body weight of the radionuclide is administered and;
• administering a therapeutic gene to said patient.