新型全自动 Trasis AiO 平台制备高比活度 Ga-FAPI-46。
New Fully Automated Preparation of High Apparent Molar Activity Ga-FAPI-46 on a Trasis AiO Platform.
机构信息
Preclinical Molecular Imaging, Division of Radiotherapy and Imaging, The Institute of Cancer Research, London SW7 3RP, UK.
Sofie, Dulles, VA 20166, USA.
出版信息
Molecules. 2022 Jan 20;27(3):675. doi: 10.3390/molecules27030675.
A large number of applications for fibroblast activation protein inhibitors (FAPI)-based PET agents have been evaluated in conditions ranging from cancer to non-malignant diseases such as myocardial infarction. In particular, Ga-FAPI-46 was reported to have a high specificity and affinity for FAP-expressing cells, a fast and high accumulation in tumor lesions/injuries together with a fast body clearance when investigated in vivo. Due to the increasing interest in the use of the agent both preclinically and clinically, we developed an automated synthesis for the production of Ga-FAPI-46 on a Trasis AiO platform. The new synthetic procedure, which included the processing of the generator eluate using a strong cation exchange resin and a final purification step through an HLB followed by a QMA cartridge, yielded Ga-FAPI-46 with high radiochemical purity (>98%) and apparent molar activity (271.1 ± 105.6 MBq/nmol). Additionally, the in vitro and in vivo properties of the product were assessed on glioblastoma cells and mouse model. Although developed for the preparation of Ga-FAPI-46 for preclinical use, our method can be adapted for clinical production as a reliable alternative to the manual (i.e., cold kit) or modular systems preparations already described in the literature.
大量基于成纤维细胞活化蛋白抑制剂(FAPI)的 PET 探针的应用已在从癌症到非恶性疾病(如心肌梗死)等多种情况下进行了评估。特别是 Ga-FAPI-46 被报道对表达 FAP 的细胞具有高特异性和亲和力,在体内研究中,它在肿瘤病变/损伤中有快速且高的积累,同时具有快速的体内清除率。由于人们对该探针在临床前和临床中的应用越来越感兴趣,我们在 Trasis AiO 平台上开发了一种用于 Ga-FAPI-46 生产的自动化合成方法。该新的合成方法包括使用强阳离子交换树脂处理发生器洗脱液,以及通过 HLB 和 QMA 柱进行最终纯化步骤,得到的 Ga-FAPI-46 具有高放射化学纯度(>98%)和明显的摩尔活性(271.1 ± 105.6 MBq/nmol)。此外,还在神经胶质瘤细胞和小鼠模型上评估了该产品的体外和体内特性。虽然该方法是为临床前应用制备 Ga-FAPI-46 而开发的,但可以适应临床生产,作为文献中已经描述的手动(即冷试剂盒)或模块化系统制备的可靠替代方法。
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