Scholarlink

Background <p>Actinium-225 radiopharmaceuticals have drawn great interest in cancer therapy due to their tumor-specific delivery of cytotoxic alpha-particles. Quality control (QC) is critical for these potent agents and there is currently no consensus for best practice of actinium-225 QC. Detection of actinium-225 (T<sub>1/2</sub> = 9.92&#xa0;days) is challenging; however, the francium-221 (T<sub>1/2</sub> = 4.8&#xa0;min, 218&#xa0;keV) and bismuth-213 (T<sub>1/2</sub> = 45&#xa0;min, 440&#xa0;keV) gamma-emitting progenies facilitate the quantification. Multiple analytical methods were investigated for limit of quantification (LOQ), radiochemical yield (RCY%), and radiochemical purity (RCP%). Those were evaluated at both francium-221 and bismuth-213 secular equilibria, and compared for accuracy and precision. While each secular equilibrium has been amply explored for actinium-225 quantification, a direct comparison between the two approaches has sparsely been examined. The RCY% was evaluated using two TLC plate readers: a gas-filled proportional counter and a plastic silicon photomultiplier detector. TLC strips were also analyzed using Liquid Scintillation Counting (LSC), High Purity Germanium (HPGe), and NaI(Tl) gamma well counting. In absence of detectable radio-impurity, HPLC RCP% were correlated to RCY%. Finally, free actinium-225 spiking recoveries were evaluated in <sup>225</sup>Ac-radiopharmaceuticals.</p> Results <p>The plastic silicon scanner resulted in RCY% differences between 30&#xa0;min and &gt; 5&#xa0;h evaluations, whereas the gas-filled proportional counter, when varying voltages, showed minor differences. Similarly, HPGe-TLC demonstrated equivalent RCY% between both equilibria. The NaI(Tl), LSC- TLC, and HPLC-gamma counting significantly underestimated RCY% or RCP% at 30&#xa0;min. Considering gamma well counting LOQ and <sup>225</sup>Ac-radiopharmaceutical low radioactive concentration, as low as 1% of free actinium-225 may be accurately detected in HPLC fractions. For TLC, LOQs were reported lower than measured in solution, free actinium-225 radioimpurity may be precisely measured as low as 0.5% of total content, except for the silicon detector.</p> Conclusion <p>Five instruments have been tested for their linearity, sensitivity, accuracy and specificity to actinium-225 quantification using francium-221 and bismuth-213 equilibria. Francium-221 equilibrium was deemed acceptable for TLC RCY% using HPGe and gas-filled proportional counter. Gamma well counting, LSC, and plastic silicon detector required bismuth-213 equilibrium for accurate RCY%. Low content free actinium-225 impurity was accurately reported for all methods except for the silicon detector. Overall, this investigation sheds light on the appropriate analytical methods for <sup>225</sup>Ac-radiopharmaceutical QC considering secular equilibrium.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Quality control of actinium-225 and 225Ac-radiopharmaceuticals: Francium-221 to be or not to be?

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月17日

查看全文
  • Miguel Toro-Gonzalez,
  • Luke Wheeless,
  • Vijai Kumar Reddy Tangadanchu,
  • Cory Hawkins,
  • Shannon Provo,
  • William Smith,
  • Michael Hommen,
  • Dan DeVries,
  • Jim Harvey,
  • Tyler Drum,
  • Diane S. Abou

摘要

Background

Actinium-225 radiopharmaceuticals have drawn great interest in cancer therapy due to their tumor-specific delivery of cytotoxic alpha-particles. Quality control (QC) is critical for these potent agents and there is currently no consensus for best practice of actinium-225 QC. Detection of actinium-225 (T1/2 = 9.92 days) is challenging; however, the francium-221 (T1/2 = 4.8 min, 218 keV) and bismuth-213 (T1/2 = 45 min, 440 keV) gamma-emitting progenies facilitate the quantification. Multiple analytical methods were investigated for limit of quantification (LOQ), radiochemical yield (RCY%), and radiochemical purity (RCP%). Those were evaluated at both francium-221 and bismuth-213 secular equilibria, and compared for accuracy and precision. While each secular equilibrium has been amply explored for actinium-225 quantification, a direct comparison between the two approaches has sparsely been examined. The RCY% was evaluated using two TLC plate readers: a gas-filled proportional counter and a plastic silicon photomultiplier detector. TLC strips were also analyzed using Liquid Scintillation Counting (LSC), High Purity Germanium (HPGe), and NaI(Tl) gamma well counting. In absence of detectable radio-impurity, HPLC RCP% were correlated to RCY%. Finally, free actinium-225 spiking recoveries were evaluated in 225Ac-radiopharmaceuticals.

Results

The plastic silicon scanner resulted in RCY% differences between 30 min and > 5 h evaluations, whereas the gas-filled proportional counter, when varying voltages, showed minor differences. Similarly, HPGe-TLC demonstrated equivalent RCY% between both equilibria. The NaI(Tl), LSC- TLC, and HPLC-gamma counting significantly underestimated RCY% or RCP% at 30 min. Considering gamma well counting LOQ and 225Ac-radiopharmaceutical low radioactive concentration, as low as 1% of free actinium-225 may be accurately detected in HPLC fractions. For TLC, LOQs were reported lower than measured in solution, free actinium-225 radioimpurity may be precisely measured as low as 0.5% of total content, except for the silicon detector.

Conclusion

Five instruments have been tested for their linearity, sensitivity, accuracy and specificity to actinium-225 quantification using francium-221 and bismuth-213 equilibria. Francium-221 equilibrium was deemed acceptable for TLC RCY% using HPGe and gas-filled proportional counter. Gamma well counting, LSC, and plastic silicon detector required bismuth-213 equilibrium for accurate RCY%. Low content free actinium-225 impurity was accurately reported for all methods except for the silicon detector. Overall, this investigation sheds light on the appropriate analytical methods for 225Ac-radiopharmaceutical QC considering secular equilibrium.