Thorium-229 quantified in historical Thorium-228 capsules

Boden, Sven; Vints, Koen; Cagno, Simone; Maertens, Dominic; Hecke, Karen Van; Cardinaels, Thomas

doi:10.1016/j.apradiso.2016.11.012

Cited by 7 publications

(6 citation statements)

References 6 publications

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“…213 Bi (7–180 MBq) was eluted from an in-house SCK CEN generator or from the 225 Ac/ 213 Bi generator provided by the European Commission–Joint Research Centre. , 213 Bi was eluted in 600 μL of 0.1 M HCl/NaI (molar apparent activity 0.8–15.8 MBq/nmol) and collected in a vial containing 120 μL of 4 M sodium acetate buffer (pH 5.5). This mixture was added to 50–100 μg of DTPA-sdAb in 0.1 M sodium acetate buffer (pH 7) and incubated for 7 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Efficacy of ²¹³Bi-labeled sdAbs in a Preclinical Model of Ovarian Cancer

et al. 2020

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Targeted alpha-particle therapy (TAT) might be a relevant therapeutic strategy to circumvent resistance to conventional therapies in the case of HER2-positive metastatic cancer. Single-domain antibody fragments (sdAb) are promising vehicles for TAT because of their excellent in vivo properties, high target affinity, and fast clearance kinetics. This study combines the cytotoxic α-particle emitter bismuth-213 ( 213 Bi) and HER2targeting sdAbs. The in vitro specificity, affinity, and cytotoxic potency of the radiolabeled complex were analyzed on HER2 pos cells. Its in vivo biodistribution through serial dissections and via Cherenkov and micro-single-photon emission computed tomography (CT)/CT imaging was evaluated. Finally, the therapeutic efficacy and potential associated toxicity of [ 213 Bi]Bi-DTPA-2Rs15d were evaluated in a HER2 pos tumor model that manifests peritoneal metastasis. In vitro, [ 213 Bi]Bi-DTPA-2Rs15d bound HER2 pos cells in a HER2-specific way. In mice, high tumor uptake was reached already 15 min after injection, and extremely low uptake values were observed in normal tissues. Co-infusion of gelofusine resulted in a 2-fold reduction in kidney uptake. Administration of [ 213 Bi]Bi-DTPA-2Rs15d alone and in combination with trastuzumab resulted in a significant increase in median survival. We describe for the very first time the successful labeling of an HER2-sdAb with the α-emitter 213 Bi, and after intravenous administration, revealing high in vivo stability and specific accumulation in target tissue and resulting in an increased median survival of these mice especially in combination with trastuzumab. These results indicate the potential of [ 213 Bi]Bi-DTPA-sdAb as a new radioconjugate for TAT, alone and as an add-on to trastuzumab for the treatment of HER2 pos metastatic cancer.

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Section: Methodsmentioning

confidence: 99%

Therapeutic Efficacy of ²¹³Bi-labeled sdAbs in a Preclinical Model of Ovarian Cancer

et al. 2020

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“…225 Ac samples were obtained from recurrent (trimestral, 6 MBq) milkings of an in-house 229 Th stock obtained from a processed 229 Th capsule as described by Boden et al ( 2017 ). Milkings were performed with the aid of a tandem system of extraction chromatography columns using TEVA and DGA columns obtained from TrisKem, France.…”

Section: Methodsmentioning

confidence: 99%

“…Using these two protocols, we evaluated the amount of unbound 213 Bi for two different chelators [ 225 Ac]Ac-DEPA(7-[2-(bis-carboxymethylamino)-ethyl]-4,10-bis-carboxymethyl-1,4,7,10-tetraazacyclododec-1-yl-acetic acid) and [ 225 Ac]Ac-DOTA (1,4,7, 10-Tetraazacyclododecane-1, 4,7,10-tetracetic acid) using iTLC strips after incubation in human serum to evaluate stability and RDE as part of QC tests after radiolabeling. Th stock obtained from a processed 229 Th capsule as described by Boden et al (2017). Milkings were performed with the aid of a tandem system of extraction chromatography columns using TEVA and DGA columns obtained from TrisKem, France.…”

Section: Introductionmentioning

confidence: 99%

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

Saint-Hubert

Ahenkorah

et al. 2022

EJNMMI radiopharm. chem.

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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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“…Two examples of 229 Th sources that can produce clinically relevant activities of 225 Ac are (1) the US Department of Energy, Oak Ridge National Laboratory (ORNL) in Oak Ridge, TN, United States of America and (2) the Directorate for Nuclear Safety and Security of the JRC of the European Commission in Karlsruhe, Germany. Additionally, at the Belgian Nuclear Research Centre (SCK CEN) in Mol, Belgium, very pure sources of 229 Th were identified, processed, and used for pre-clinical studies [ 20 ]. The total global annual 225 Ac production volume is approximately 55–65 GBq [ 21 ] and cannot meet the growing demand for 225 Ac, but interestingly, it has been reported that stocks will increase by extraction of additional 229 Th from US legacy wastes [ 7 ].…”

Section: Radionuclide Properties and Production Of 225 Ac And Its Daughter 213 Bimentioning

confidence: 99%

Bismuth-213 for Targeted Radionuclide Therapy: From Atom to Bedside

et al. 2021

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In contrast to external high energy photon or proton therapy, targeted radionuclide therapy (TRNT) is a systemic cancer treatment allowing targeted irradiation of a primary tumor and all its metastases, resulting in less collateral damage to normal tissues. The α-emitting radionuclide bismuth-213 (213Bi) has interesting properties and can be considered as a magic bullet for TRNT. The benefits and drawbacks of targeted alpha therapy with 213Bi are discussed in this review, covering the entire chain from radionuclide production to bedside. First, the radionuclide properties and production of 225Ac and its daughter 213Bi are discussed, followed by the fundamental chemical properties of bismuth. Next, an overview of available acyclic and macrocyclic bifunctional chelators for bismuth and general considerations for designing a 213Bi-radiopharmaceutical are provided. Finally, we provide an overview of preclinical and clinical studies involving 213Bi-radiopharmaceuticals, as well as the future perspectives of this promising cancer treatment option.

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Thorium-229 quantified in historical Thorium-228 capsules

Cited by 7 publications

References 6 publications

Therapeutic Efficacy of ²¹³Bi-labeled sdAbs in a Preclinical Model of Ovarian Cancer

Therapeutic Efficacy of ²¹³Bi-labeled sdAbs in a Preclinical Model of Ovarian Cancer

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

Bismuth-213 for Targeted Radionuclide Therapy: From Atom to Bedside

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Thorium-229 quantified in historical Thorium-228 capsules

Cited by 7 publications

References 6 publications

Therapeutic Efficacy of 213Bi-labeled sdAbs in a Preclinical Model of Ovarian Cancer

Therapeutic Efficacy of 213Bi-labeled sdAbs in a Preclinical Model of Ovarian Cancer

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

Bismuth-213 for Targeted Radionuclide Therapy: From Atom to Bedside

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Therapeutic Efficacy of ²¹³Bi-labeled sdAbs in a Preclinical Model of Ovarian Cancer

Therapeutic Efficacy of ²¹³Bi-labeled sdAbs in a Preclinical Model of Ovarian Cancer