Alpha Radionuclides More Effective than Zevalin for NHL - In Mice

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Blood First Edition Paper, prepublished online May 29, 2007

PubMed

Submitted January 8, 2007

Accepted May 25, 2007

Targeted cancer therapy with a novel low dose rate alpha-emitting

radioimmunoconjugate

Jostein Dahle*, n Borrebaek, Thora J. Jonasdottir, Anne

e Hjelmerud, Katrine B. Melhus, Oyvind S. Bruland, Oliver W.

Press, and Roy H. Larsen

Department of Radiation Biology, The Norwegian Radium Hospital,

Oslo, Norway

Research and Development, Algeta ASA, Oslo, Norway

Small Animal Section, Department of Companion Animal Clinical

Sciences, Norwegian School of Veterinary Science, Oslo, Norway

University of Oslo, & Department of Oncology, The Norwegian Radium

Hospital, Oslo, Norway

Department of Clinical Research, Fred Hutchinson Cancer Research

Center, Seattle, WA, United States

Alpha-emitting radionuclides are highly cytotoxic and are of

considerable interest in the treatment of cancer. A particularly

interesting approach is in radioimmunotherapy. However, -emitting

antibody conjugates have been difficult to exploit clinically due to

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 -

particle emitting nuclide 227Th, exemplified here using the

monoclonal antibody rituximab. In vitro, this radioimmunoconjugate

killed lymphoma cells at 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 Bq/g levels without apparent

toxicity. Therapy with 227Th-rituximab was significantly more

effective than the control radioimmunoconjugate 227Th-trastuzumab

and the standard -emitting radioimmunoconjugate for CD20 positive

lymphoma, Zevalin® (90Y-tiuxetan-ibritumomab).

Thorium-227 based constructs may provide a novel approach for

targeted therapy against a wide variety of cancers.

* The unit of radioactive decay equal to 1 disintegration per second

per milliliter. 37 billion (3.7x10 10 ) becquerels = 1 curie (Ci),

which is what one gram of radium puts out.