Coded aperture and Compton imaging for the development of 225Ac-based radiopharmaceuticals

Background: Targeted alpha-particle therapy (TAT) has great promise as a cancer treatment. Arguably the most promising TAT radionuclide that has been proposed is Ac-225. The development of Ac-225-based radiopharmaceuticals has been hampered due to the lack of effective means to study the daughter redistribution of these agents in small animals at the preclinical stage.Purpose: The ability to directly image the daughters, namely Fr-221 and Bi-213, via their gamma-ray emissions would be a boon for preclinical studies. That said, conventional medical imaging modalities, including single photon emission computed tomography (SPECT) based on nonmultiplexed collimation, cannot be employed due to sensitivity limitations.Methods: As an alternative, we propose the use of both coded aperture and Compton imaging with the former modality suited to the 218-keV gamma-ray emission of Fr-221 and the latter suited to the 440-keV gamma-ray emission of Bi-213.Results: This work includes coded aperture images of Fr-221 and Compton images of Bi-213 in tumor-bearing mice injected with Ac-225-based radiopharmaceuticals.Conclusions: These results are the first demonstration of visualizing and quantifying the Ac-225 daughters in small animals through the application of coded aperture and Compton imaging.