Targeted alpha particle therapy using actinium-225 conjugates

A method of treating cancerous cells with alpha particles in an individual in need of such treatment comprising the step of:

• administering a pharmacologically effective dose of an 225Ac conjugate comprising a functionalized chelant having the structure
• 11
• wherein R is independently CHQCO2X;
• Q is independently hydrogen;
• C1-C4 alkyl or (C1-C2 alkyl) phenyl;
• X is independently hydrogen;
• benzyl or C1-C4 alkyl;
• Z1 is (CH2)nY wherein n is 1 to 10 and Y is an electrophilic or nucleophilic moiety and Z2 is R;
• or, in the alternative,
• Z1 is hydrogen and Z2 is a peptide linker composed of 1-10 amino acids;
• said Y or said peptide linker covalently attached to an antibody or fragment thereof, or other biologic molecule;
• or a pharmaceutically acceptable salt thereof, complexed with 225Ac;
• wherein said antibody or fragment thereof, or other biologic molecule binds to said cancer cells, said 225Ac or its daughters emitting said alpha particles into said cancerous cells, wherein said alpha particles cause a cytotoxic effect on said cancerous cells, thereby effecting treatment of said individual.

A method of treating cancerous cells with alpha particles in an individual in need of such treatment comprising:

• administering a pharmacologically effective dose of an 225Ac conjugate comprising a functionalized chelant having the structure
• 12
• wherein R and Z2 are CO2H;
• and
• Z1 is (CH2)nY wherein n is 1 to 10 and Y is an electrophilic or nucleophilic moiety;
• said Y covalently attached to a monoclonal antibody;
• or a pharmaceutically acceptable salt thereof;
• complexed with 225Ac;
• binding said monoclonal antibody to said cancerous cells;
• internalizing said 225Ac within said cancerous cells, and
• emitting said alpha particles from said 225Ac or its daughters, said alpha particles remaining within said cancerous cells, wherein said alpha particles cause a cytoxic effect on said cancerous cells thereby effecting treatment of said individual.