Targeted cancer therapy with a novel low-dose rate α-emitting radioimmunoconjugate

alpha-emitting radionuclides are highly cytotoxic and are of considerable interest in the treatment of cancer. A particularly interesting approach is in radioimmunotherapy. However, a-emitting antibody conjugates have been difficult to exploit clinically due to the short half-life of the radionuclides, low production capability, or limited source materials. We have developed a novel technology based on the low-dose rate a-particle-emitting nuclide Th-227, exemplified here using the monoclonal antibody rituximab. In vitro, this radioimmunoconjugate killed lymphoma cells at Becquerel per milliliter (Bq/mL) levels. A single injection of (227)Thrituximab induced complete tumor regression in up to 60% of nude mice bearing macroscopic (32-256 mm(3)) human B-lymphoma xenografts at Becquerel per gram (Bq/g) levels without apparent toxicity. Therapy with Th-227-rituximab was significantly more effective than the control radioimmuno-conjugate Th-227-trastuzumab and the standard (beta-emitting radioimmunoconjugate for CD20(+) lymphoma, 9 Ytiuxetan-ibritumomab. Thorium-227 based constructs may provide a novel approach for targeted therapy against a wide variety of cancers.