PDF(Pubmed)
Abstract：
BACKGROUND: The Affibody molecule, ABY-025, has demonstrated utility to detect human epidermal growth factor receptor 2 (HER2) in vivo, either radiolabelled with indium-111 (111In) or gallium-68 (68Ga). Using the latter, 68Ga, is preferred due to its use in positron emission tomography with superior resolution and quantifying capabilities in the clinical setting compared to 111In. For an ongoing phase II study (NCT05619016) evaluating ABY-025 for detecting HER2-low lesions and selection of patients for HER2-targeted treatment, the aim was to optimize an automated and cGMP-compliant radiosynthesis of [68Ga]Ga-ABY-025. [68Ga]Ga-ABY-025 was produced on a synthesis module, Modular-Lab PharmTracer (Eckert & Ziegler), commonly used for 68Ga-labelings. The radiotracer has previously been radiolabeled on this module, but to streamline the production, the method was optimized. Steps requiring manual interactions to the radiolabeling procedure were minimized including a convenient and automated pre-concentration of the 68Ga-eluate and a simplified automated final formulation procedure. Every part of the radiopharmaceutical production was carefully developed to gain robustness and to avoid any operator bound variations to the manufacturing. The optimized production method was successfully applied for 68Ga-labeling of another radiotracer, verifying its versatility as a universal and robust method for radiosynthesis of Affibody-based peptides.
RESULTS: A simplified and optimized automated cGMP-compliant radiosynthesis method of [68Ga]Ga-ABY-025 was developed. With a decay corrected radiochemical yield of 44 ± 2%, a radiochemical purity (RCP) of 98 ± 1%, and with an RCP stability of 98 ± 1% at 2 h after production, the method was found highly reproducible. The production method also showed comparable results when implemented for radiolabeling another similar peptide.
CONCLUSIONS: The improvements made for the radiosynthesis of [68Ga]Ga-ABY-025, including introducing a pre-concentration of the 68Ga-eluate, aimed to utilize the full potential of the 68Ge/68Ga generator radioactivity output, thereby reducing radioactivity wastage. Furthermore, reducing the number of manually performed preparative steps prior to the radiosynthesis, not only minimized the risk of potential human/operator errors but also enhanced the process\' robustness. The successful application of this optimized radiosynthesis method to another similar peptide underscores its versatility, suggesting that our method can be adopted for 68Ga-labeling radiotracers based on Affibody molecules in general.
BACKGROUND: NCT, NCT05619016, Registered 7 November 2022, https://clinicaltrials.gov/study/NCT05619016?term=HER2&cond=ABY025&rank=1.
RESULTS: A simplified and optimized automated cGMP-compliant radiosynthesis method of [68Ga]Ga-ABY-025 was developed. With a decay corrected radiochemical yield of 44 ± 2%, a radiochemical purity (RCP) of 98 ± 1%, and with an RCP stability of 98 ± 1% at 2 h after production, the method was found highly reproducible. The production method also showed comparable results when implemented for radiolabeling another similar peptide.
CONCLUSIONS: The improvements made for the radiosynthesis of [68Ga]Ga-ABY-025, including introducing a pre-concentration of the 68Ga-eluate, aimed to utilize the full potential of the 68Ge/68Ga generator radioactivity output, thereby reducing radioactivity wastage. Furthermore, reducing the number of manually performed preparative steps prior to the radiosynthesis, not only minimized the risk of potential human/operator errors but also enhanced the process\' robustness. The successful application of this optimized radiosynthesis method to another similar peptide underscores its versatility, suggesting that our method can be adopted for 68Ga-labeling radiotracers based on Affibody molecules in general.
BACKGROUND: NCT, NCT05619016, Registered 7 November 2022, https://clinicaltrials.gov/study/NCT05619016?term=HER2&cond=ABY025&rank=1.
摘要：
背景：适体分子，ABY-025已证明可在体内检测人表皮生长因子受体2（HER2），用铟-111(111In)或镓-68(68Ga)放射性标记。使用后者，68Ga,是优选的，因为与111In相比，它在临床环境中具有更高的分辨率和量化能力。对于正在进行的II期研究（NCT05619016），评估ABY-025检测HER2低病变并选择HER2靶向治疗的患者，目的是优化[68Ga]Ga-ABY-025的自动化和符合cGMP的放射合成。[68Ga]Ga-ABY-025在合成模块上产生，模块化实验室PharmTracer(Eckert&Ziegler),常用于68Ga标签。放射性示踪剂先前已在该模块上进行了放射性标记，但是为了简化生产，方法进行了优化。将需要手动与放射性标记程序相互作用的步骤最小化,包括68Ga洗脱物的方便且自动化的预浓缩和简化的自动化最终配制程序。放射性药物生产的每个部分都经过精心开发，以获得坚固性并避免任何操作员对制造的限制变化。优化的生产方法已成功应用于另一种放射性示踪剂的68Ga标记，验证其多功能性作为放射合成基于Affibody的肽的通用和强大的方法。
结果：开发了一种简化和优化的自动cGMP兼容放射合成方法[68Ga]Ga-ABY-025。衰变校正的放射化学产率为44±2%，放射化学纯度（RCP）为98±1％，生产后2小时的RCP稳定性为98±1%，该方法具有很高的重现性。当实施放射性标记另一种类似的肽时,生产方法也显示出相当的结果。
结论：[68Ga]Ga-ABY-025放射性合成的改进，包括引入预浓缩的68Ga-洗脱液，旨在利用68Ge/68Ga发生器放射性输出的全部潜力，从而减少放射性浪费。此外，减少放射合成之前手动进行的制备步骤的数量，不仅最小化了潜在的人/操作员错误的风险，而且增强了过程的鲁棒性。这种优化的放射合成方法成功应用于另一种类似的肽强调了其多功能性，这表明我们的方法可用于基于Affibody分子的68Ga标记放射性示踪剂。
背景：NCT，NCT05619016，2022年11月7日注册，https://clinicaltrials.gov/study/NCT05619016?term=HER2&cond=ABY025&rank=1。
结果：开发了一种简化和优化的自动cGMP兼容放射合成方法[68Ga]Ga-ABY-025。衰变校正的放射化学产率为44±2%，放射化学纯度（RCP）为98±1％，生产后2小时的RCP稳定性为98±1%，该方法具有很高的重现性。当实施放射性标记另一种类似的肽时,生产方法也显示出相当的结果。
结论：[68Ga]Ga-ABY-025放射性合成的改进，包括引入预浓缩的68Ga-洗脱液，旨在利用68Ge/68Ga发生器放射性输出的全部潜力，从而减少放射性浪费。此外，减少放射合成之前手动进行的制备步骤的数量，不仅最小化了潜在的人/操作员错误的风险，而且增强了过程的鲁棒性。这种优化的放射合成方法成功应用于另一种类似的肽强调了其多功能性，这表明我们的方法可用于基于Affibody分子的68Ga标记放射性示踪剂。
背景：NCT，NCT05619016，2022年11月7日注册，https://clinicaltrials.gov/study/NCT05619016?term=HER2&cond=ABY025&rank=1。
