Dataset Information

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.

SUBMITTER: Castillo Seoane D

PROVIDER: S-EPMC9588853 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Castillo Seoane Dayana D De Saint-Hubert Marijke M Ahenkorah Stephen S Saldarriaga Vargas Clarita C Ooms Maarten M Struelens Lara L Koole Michel M

EJNMMI radiopharmacy and chemistry 20221023 1

<h4>Background</h4>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 actiniu ...[more]

PMID: 36274098

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Project description:BackgroundThe liver is a common site for metastatic disease for a variety of cancers, including colorectal cancer. Both primary and secondary liver tumors are supplied through the hepatic artery while the healthy liver is supplied by the portal vein. Transarterial radioembolization (TARE) using yttrium-90 glass or resin microspheres have shown promising results with reduced side-effects but have similar survival benefits as chemoembolization in patients with hepatocellular carcinoma (HCC). This highlights the need for new novel agents against HCC. Targeted alpha therapy (TAT) is highly potent treatment due to the short range (sparing adjacent normal tissue), and densely ionizing track (high linear energy transfer) of the emitted α-particles. The incorporation of α-particle-emitting radioisotopes into treatment of HCC has been extremely limited, with our recent publication pioneering the field of α-particle-emitting TARE (αTARE). This study focuses on an in-depth evaluation of the αTARE-agent [225Ac]Ac-DOTA-TDA-Lipiodol® as an effective therapeutic agent against HCC regarding pharmacokinetics, dosimetry, stability, and therapeutic efficacy.Results[225Ac]Ac-DOTA-TDA was shown to be a highly stable with bench-top stability at ≥ 95% radiochemical purity (RCP) over a 3-day period and serum stability was ≥ 90% RCP over 5-days. The pharmacokinetic data showed retention in the tumor of [225Ac]Ac-DOTA-TDA-Lipiodol® and clearance through the normal organs. In addition, the tumor and liver acted as suppliers of the free daughters, which accumulated in the kidneys supplied via the blood. The dose limiting organ was the liver, and the estimated maximum tolerable activity based on the rodents whole-body weight: 728-3641 Bq/g (male rat), 396-1982 Bq/g (male mouse), and 453-2263 Bq/g (female mouse), depending on an RBE-value (range 1-5). Furthermore, [225Ac]Ac-DOTA-TDA-Lipiodol® showed significant improvement in survival for both the male and female mice (median survival 47-days) compared with controls (26-days untreated, and 33-35-days Lipiodol® alone).ConclusionsThis study shows that [225Ac]Ac-DOTA-TDA-Lipiodol® is a stable compound allowing for centralized manufacturing and distribution world-wide. Furthermore, the result of this study support the continue development of evaluation of the αTARE-agent [225Ac]Ac-DOTA-TDA-Lipiodol® as a potential treatment option for treating hepatic tumors.

Project description:AimOver recent years, [225Ac]Ac-PSMA and [177Lu]Lu-PSMA radiopharmaceutical therapy have evolved as a promising treatment option for advanced prostate cancer. Especially for alpha particle emitter treatments, there is still a need for improving dosimetry, which requires accurate values of relative biological effectiveness (RBE). To achieve that, consideration of DNA damages in the cell nucleus and knowledge of the energy deposition in the location of the DNA at the nanometer scale are required. Monte Carlo particle track structure simulations provide access to interactions at this level. The aim of this study was to estimate the RBE of 225Ac compared to 177Lu. The initial damage distribution after radionuclide decay and the residual damage after DNA repair were considered.MethodsThis study employed the TOol for PArtcile Simulation (TOPAS) based on the Geant4 simulation toolkit. Simulation of the nuclear DNA and damage scoring were performed using the TOPAS-nBio extension of TOPAS. DNA repair was modeled utilizing the Python-based program MEDRAS (Mechanistic DNA Repair and Survival). Five different cell geometries of equal volume and two radionuclide internalization assumptions as well as two cell arrangement scenarios were investigated. The radionuclide activity (number of source points) was adopted based on SPECT images of patients undergoing the above-mentioned therapies.ResultsBased on the simulated dose-effect curves, the RBE of 225Ac compared to 177Lu was determined in a wide range of absorbed doses to the nucleus. In the case of spherical geometry, 3D cell arrangement and full radionuclide internalization, the RBE based on the initial damage had a constant value of approximately 2.14. Accounting for damage repair resulted in RBE values ranging between 9.38 and 1.46 for 225Ac absorbed doses to the nucleus between 0 and 50 Gy, respectively.ConclusionIn this work, the consideration of DNA repair of the damage from [225Ac]Ac-PSMA and [177Lu]Lu-PSMA revealed a dose dependency of the RBE. Hence, this work suggested that DNA repair is an important aspect to understand response to different radiation qualities.

Dataset Information

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

Background

Results

Conclusion

Publications

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

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

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

Background

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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