Publication Date:
2007-09-15
Description:
α-emitting radionuclides are highly cytotoxic and are of considerable interest in the treatment of cancer. A particularly interesting approach is in radioimmunotherapy. However, α-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 α-particle–emitting nuclide 227Th, 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 227Th-rituximab induced complete tumor regression in up to 60% of nude mice bearing macroscopic (32-256 mm3) human B-lymphoma xenografts at Becquerel per gram (Bq/g) levels without apparent toxicity. Therapy with 227Th-rituximab was significantly more effective than the control radioimmunoconjugate 227Th-trastuzumab and the standard β-emitting radioimmunoconjugate for CD20+ lymphoma90Y-tiuxetan-ibritumomab. Thorium-227 based constructs may provide a novel approach for targeted therapy against a wide variety of cancers.
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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