Gamma counting protocols for the accurate quantification of 225Ac and 213Bi without the need for a secular equilibrium between parent and gamma-emitting daughter

Abstract

Background Quantification of actinium-225 through gamma counter measurements, when there is no secular equilibrium between actinium-225 and its gamma emitting daughters bismuth-213 and/or francium-221, can provide valuable information regarding the possible relocation of recoiled daughters such that related radiotoxicity effects can be evaluated. This study proposes a multiple time-point protocol using the bismuth-213 photopeak with measurements before secular equilibrium between actinium-225 and bismuth-213, and a single time-point protocol using both the francium-221 and bismuth-213 photopeak while assuming secular equilibrium between actinium-225 and francium-221 but not between bismuth-213 and actinium-225. Results Good agreement (i.e. 3% accuracy) was obtained when relying on a multiple time-points measurement of bismuth-213 to quantify both actinium-225 and excess of bismuth-213. Following scatter correction, actinium-225 can be accurately quantified using the francium-221 in a single time-point measurement within 3% of accuracy. The analysis performed on the stability data of [225Ac]Ac-DEPA and [225Ac]Ac-DOTA complexes, before secular equilibrium between bismuth-213 and actinium-225 was formed, revealed considerable amounts of unbound bismuth-213 (i.e. more than 90%) after 24 h of the radiolabeling most likely due to the recoiled daughter effect. Conclusion Both protocols were able to accurately estimate 225Ac-activities provided the francium-221 energy window was corrected for the down scatter of the higher-energy gamma-emissions by bismuth-213. This could prove beneficial to study the recoiled daughter effect and redistribution of free bismuth-213 by monitoring the accumulation or clearance of bismuth-213 in different tissues during biodistribution studies or in patient samples during clinical studies. On the other hand, the single gamma counter measurement protocol, although required a 30 min waiting time, is more time and cost efficient and therefore more appropriate for standardized quality control procedures of 225Ac-labeled radiopharmaceuticals.

Actinium-225 targeted alpha particle therapy for prostate cancer

“…Since the daughters 213 Bi and 221 Fr take different times to reach secular equilibrium with 225 Ac, quantification of 225 Ac using 213 Bi and 221 Fr before equilibrium or in case of 213 Bi redistribution is challenging. In this regard, to determine the 225 Ac amount, Seone et al developed a multi-time point gamma counting of 213 Bi (before secular equilibrium), and single time-point gamma counting of 213 Bi and 221 Fr considering no secular equilibrium 93 . Along with this, one major quality control concern related to accelerator produced 225 Ac via spallation of 232 Th is an impurity of long lived 227 Ac.…”

Implementing Ac-225 labelled radiopharmaceuticals: practical considerations and (pre-)clinical perspectives

“…5 , underlining the importance for the onset of the equilibrium after > 30 min when performing measurements in specific energy windows. Algorithms are available for adapting for the ingrowth of the equilibrium; however, these methods do not consider the different chemical forms that are present (Castillo Seoane et al 2022 ).

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