Wang Binchen, Jiang Yaqun, Zhu Jiaxu, Wu Huiqin, Wu Jianyuan, Li Ling, Huang Jianying, Xiao Zhiwei, He Yong
Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
Clinical Trial Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Front Oncol. 2024 Aug 2;14:1445415. doi: 10.3389/fonc.2024.1445415. eCollection 2024.
The αβ-integrin targeting trimeric ligand [Ga]Ga-Trivehexin has emerged as a promising candidate for clinical application due to its clinical imaging potentials in various malignant cancers. Our objective was to develop a simplified and reproducible module-based automated synthesis protocol to expand its availability in clinical application.
The pH value and the precursor load of radiolabeling were explored using an iQS-TS fully-automated module. Radiochemical purity was evaluated by radio-HPLC and radio-TLC. The ethanol content, radionuclide purity and identity, bacterial endotoxins, sterility, and stability of the final product [Ga]Ga-Trivehexin were all tested. Biodistribution of [Ga]Ga-Trivehexin in healthy volunteers was also conducted.
The synthesis was explored and established using fully-automated module with outstanding radiochemical purity (>99%). Considering molar activity and economic costs, a pH of 3.6 and precursor dose of 30 μg were determined to be optimal. All relevant quality control parameters were tested and met the requirement of European Pharmacopoeia. stability test and imaging in healthy volunteer indicated the practical significance in clinical routines.
A fully-automated synthesis protocol for [Ga]Ga-Trivehexin using the iQS-TS synthesis module was achieved and conformed to the clinical quality standards.
ClinicalTrials.gov, NCT05835570. Registered 28 April 2023, https://www.clinicaltrials.gov/study/NCT05835570.
αβ整合素靶向三聚体配体[镓]镓-三己新因其在多种恶性肿瘤中的临床成像潜力，已成为临床应用中一个有前景的候选药物。我们的目标是开发一种简化且可重复的基于模块的自动化合成方案，以扩大其在临床应用中的可用性。
使用iQS-TS全自动模块探索放射性标记的pH值和前体负载量。通过放射性高效液相色谱法和放射性薄层层析法评估放射化学纯度。对最终产物[镓]镓-三己新的乙醇含量、放射性核素纯度和同一性、细菌内毒素、无菌性及稳定性均进行了检测。还对[镓]镓-三己新在健康志愿者体内的生物分布进行了研究。
使用全自动模块探索并建立了合成方法，放射化学纯度优异（>99%）。综合考虑摩尔活度和经济成本，确定pH值为3.6、前体剂量为30μg为最佳条件。所有相关质量控制参数均经过检测，符合欧洲药典要求。稳定性测试和在健康志愿者体内的成像表明其在临床常规应用中的实际意义。
使用iQS-TS合成模块实现了[镓]镓-三己新的全自动合成方案，且符合临床质量标准。
ClinicalTrials.gov，NCT05835570。于2023年4月28日注册，https://www.clinicaltrials.gov/study/NCT05835570。
