Dayana Castillo Seoane1,2, Marijke De Saint-Hubert3, Stephen Ahenkorah4,5, Clarita Saldarriaga Vargas3,6, Maarten Ooms4, Lara Struelens3, Michel Koole7. 1. Unit of Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, Katholieke Universiteit Leuven (KUL), Louvain, Belgium. marijke.de.saint-hubert@sckcen.be. 2. Research Unit in Dosimetric Applications, Belgian Nuclear Research Centre (SCK CEN), Mol, Belgium. marijke.de.saint-hubert@sckcen.be. 3. Research Unit in Dosimetric Applications, Belgian Nuclear Research Centre (SCK CEN), Mol, Belgium. 4. NURA Research Group, Belgian Nuclear Research Center (SCK CEN), Mol, Belgium. 5. Unit of Radiopharmaceutical Research, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven (KUL), Louvain, Belgium. 6. Department of Medical Imaging, Laboratory for In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel (VUB), Brussels, Belgium. 7. Unit of Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, Katholieke Universiteit Leuven (KUL), Louvain, Belgium.
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.
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.
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