Targeted Alpha-Particle Therapy with 227Th-Labeled Antibodies

Jostein      Dahle; Roy   H.   Larsen

doi:10.2174/1874471010801030209

Abstract

A novel technology for preparing low dose rate alpha-radioimmunoconjugates has recently been developed based on the actinide radionuclide 227Th (T1/2=18.7 days). Thorium-227 has interesting properties that can be exploited in radioimmunotherapy: (1) it can be conjugated in stable fashion to antibodies using bifunctional DOTA; (2) it can be produced in virtually unlimited amounts with current technology; (3) it has a half-life suitable for central production and long distance shipment; (4) the alpha-particle released during decay has an average energy of 5.9 MeV, which is well suited for inactivation of tumor cells; (5) the in vivo fate of its radioactive daughter product in terms of distribution and toxicity is well known in animals as well as in humans. This review presents in vitro and in vivo preclinical results obtained using 227Th conjugated to the monoclonal antibodies rituximab and trastuzumab.

Keywords: Alpha-particle radiation, radioimmunotherapy, thorium-227, rituximab, trastuzumab

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