Recent renewed interest in radium-224 (224Ra) as a radiotherapeutic agent prompted the development of a primary standard for activity at the National Institute of Standards and Technology (NIST). The 224Ra decay chain includes the emission four alpha particles and two high-energy beta particles, terminating with stable 208Pb. Deployed as a radiopharmaceutical, this results in a high dose over a very short range in tissue, making 224Ra appealing for the treatment of minimum residual disease (e.g., micrometastases, tumor margins). Literature descriptions of the elution of 224Ra from a 228Th generator claim negligible breakthrough. Measuring samples by high-purity germanium (HPGe) gamma-ray spectrometry after more than ten 224Ra half-lives has revealed higher-than-expected and significantly variable levels of 228Th breakthrough, prompting us to explore the sensitivity of various methods for identifying and quantifying breakthrough in this decay chain. The measurements are complicated by the fact that photon emissions from 228Th and 224Ra are small compared to the emissions from their progeny. We discuss the well-known challenges of detecting 228Th breakthrough via gamma-ray spectrometry, and present minimum detectable activities (MDAs) for 228Th measured at different time-points so that Compton contributions from 224Ra and its progeny vary over several orders of magnitude. Because of these challenges, researchers often point to half-life determinations as a means of excluding impurities/breakthrough. We present measurements and Monte Carlo calculations for liquid scintillation (LS) counting, ionization chamber, and gamma-ray spectrometry determinations of the 224Ra half-life. We consider the sensitivity of the various measurements to 228Th breakthrough, showing that breakthrough must be much greater than typically claimed in order to be observed on timescales (e.g. five 224Ra half-lives) much longer than might be clinically relevant. Alternative methods for detection of 228Th breakthrough are discussed.

228Th breakthrough in 224Ra samples: what can we know and when can we know it?

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.