In Vitro and In Vivo Efficacy of a Novel CD33-Targeted Thorium-227 Conjugate for the Treatment of Acute Myeloid Leukemia.

The clinical efficacy of the first approved alpha pharmaceutical, Xofigo (radium-223 dichloride, RaCl), has stimulated significant interest in the development of new alpha-particle emitting drugs in oncology. Unlike radium-223 (Ra), the parent radionuclide thorium-227 (Th) is able to form highly stable chelator complexes and is therefore amenable to targeted radioimmunotherapy. We describe the preparation and use of a CD33-targeted thorium-227 conjugate (CD33-TTC), which binds to the sialic acid receptor CD33 for the treatment of acute myeloid leukemia (AML).

Targeted alpha therapy with 227Th-trastuzumab of intraperitoneal ovarian cancer in nude mice.

Unlabelled: The aim of the current study was to investigate the therapeutic effect of 227Th-radioimmunotherapy on intraperitoneally growing human bioluminescent HER2 positive ovarian cancer cells.

Methods: In vitro toxicity of 227Th-trastuzumab in bioluminescent SKOV3-luc-D3 ovarian cancer cells was assessed in a growth assay. The biodistribution of intraperitoneally administrated 227Th-trastuzumab in athymic nude mice without tumor cells was determined.