Synthesis and evaluation of a water-soluble polymer to reduce Ac-225 daughter migration

The actinium decay chain has been promoted as an in vivo alpha generator for therapy, but migration of daughters from the primary conjugate has lead to increased toxicity away from the target organ. To reduce daughter migration, polyethylenimine (PEI) was used with a primary chelator and secondary chelators. The primary chelator, DOTA, was used to coordinate 225 Actinium and secondary chelators-acetate and DTPA, were added to the polymer for coordination of daughters formed by decay. The (225)Actinium polymer derivatives containing secondary chelators were found to retain radioactive daughters better than the 225 Actinium bond to the primary alone. The retention of (213)Bismuth and (209)Thallium had the following order from highest retained to lowest DOTA-PEI-DTPA approximate to DOTA-PEI-CH2OO- > DOTA-PEI. The data suggests this polymer approach could be used to reduce daughter migration and has potential for development of actinium labeled radiopharmaceuticals. Copyright (c) 2007 John Wiley & Sons, Ltd.