Dosimetry for Ac-225 and Bi-213 labeled cancer therapy agents.

Introduction: We are evaluating a number of labeled agents against breast and lung cancer, to be labeled with either Ac-225 or Bi-213 labeled agents. Generator produced Ac-225 contains trace levels of Ac-227, which complicates the dosimetry and waste management. Labeling only with the shorter lived Bi-213 necessitates administering higher levels of activity.

Methods: Our data indicates that an overall whole body biological half-time of 3 hours dominates the biokinetics of our key therapeutic agents. Further studies in patients will further delineate individual organ uptakes and clearance. For now, basic biokinetic behavior was established, based on this currently measured assumption. Dose estimates for all organs for Ac-225 and all progeny were established using the OLINDA/EXM v 2.2 software. Then, dose estimates for only Bi-213 and progeny were calculated separately. Doses were given in mSv per MBq of administered activity, assuming a radiation weighting factor for alpha particles of 5.

Results: Doses were of course higher with Ac-225 (/227) with progeny than with only the Bi-213 series. Thus more activity would need to be given with the latter to achieve a good therapeutic benefit, but without the influence of the Ac-227 contaminant.

Conclusions: Ac-225 and Bi-213 labeled therapy agents are exciting new agents to achieve therapeutic benefits in patients with various forms of cancer. The radiation dosimetry methods are well defined and implemented in the OLINDA/EXM software; final dosimetry depends on obtaining data in animal or human trials to establish the biokinetics.