Daniel Thomas, Balouzet Ravinet Clara, Clerc Jérôme, Batista Rui, Mouraeff Yvan
Cochin Hospital, Assistance Publique Hôpitaux de Paris, 123 Boulevard de Port Royal, 75014, Paris, France.
EJNMMI Radiopharm Chem. 2023 Feb 7;8(1):4. doi: 10.1186/s41181-023-00187-2.
[Ga]Ga-PentixaFor is a promising radiotracer for positron emission tomography imaging of several human tumors overexpressing the chemokine receptor-4 (CXCR4). CXCR4 overexpression has been demonstrated in patients with hematologic malignancies, solid cancers, as well as cardiovascular pathologies of inflammatory origins. However, its radio synthesis is not yet fully developed in France, and existing methods do not use our type of synthesis module. Therefore, we aimed at developing a [Ga]Ga-PentixaFor synthesis with Gaia/Luna Elysia-Raytest module to use it in clinical purpose.
12 syntheses were carried out by varying the temperature conditions and radiolabeling times, and led to choose specific labelling conditions with the Gaia/Luna Elysia-Raytest module: 97 °C, 4 min. The mean synthesis time of the 3 validation runs under good manufacturing practice (GMP) was 24 min 27 s (± 8 s), and the mean radiochemical yield was 87.0% [standard deviation (SD) 6.67%]. Different quality control parameters were also evaluated in accordance with European Pharmacopeia: radiochemical and radionuclidic purity, pH, sterility, stability and endotoxins levels. The average radiochemical purity was 99.1% (SD 0.25%) assessed by instant thin layer chromatography and 99.8% (SD 0.092%) assessed by high pressure liquid chromatography. average [Ge] breakthrough was 1.48 × 10%, under the recommended level of 0.001%. We assessed the stability of the radiotracer up to 4 h at room temperature (no augmentation of the [Ga] chloride in the final product, i.e. radiochemical purity (RCP) > 98.5%). The endotoxins levels were < 5 EU/mL, and the pH was 6.5 (same for the three syntheses).
The [Ga]Ga-PentixaFor synthesis process developed on the Gaia/Luna Elysia-Raytest module has fulfilled all acceptance criteria for injectable radiopharmaceutical products regarding the European Pharmacopeia. The radiochemical purity, stability, efficacy, as well as the microbiological quality of the three GMP batches were found to be good. The robustness of the synthesis process may be suitable for multi-dose application in clinical settings.
[镓]镓-喷替沙福是一种有前景的放射性示踪剂，用于对几种过表达趋化因子受体-4（CXCR4）的人类肿瘤进行正电子发射断层显像。CXCR4过表达已在血液系统恶性肿瘤、实体癌以及炎症性心血管疾病患者中得到证实。然而，其放射性合成在法国尚未完全成熟，现有方法未使用我们这种类型的合成模块。因此，我们旨在利用盖亚/卢娜Elysia - Raytest模块开发一种[镓]镓-喷替沙福合成方法，以便用于临床。
通过改变温度条件和放射性标记时间进行了12次合成，从而确定了使用盖亚/卢娜Elysia - Raytest模块的特定标记条件：97℃，4分钟。在良好生产规范（GMP）下进行的3次验证运行的平均合成时间为24分27秒（±8秒），平均放射化学产率为87.0%[标准差（SD）6.67%]。还根据欧洲药典评估了不同的质量控制参数：放射化学和放射性核素纯度、pH值、无菌性、稳定性和内毒素水平。通过即时薄层色谱法评估的平均放射化学纯度为99.1%（SD 0.25%），通过高压液相色谱法评估为99.8%（SD 0.092%）。平均[锗]突破为1.48×10%，低于推荐水平0.001%。我们评估了放射性示踪剂在室温下长达4小时的稳定性（最终产品中[镓]氯化物无增加，即放射化学纯度（RCP）>98.5%）。内毒素水平<5 EU/mL，pH值为6.5（三次合成均相同）。
利用盖亚/卢娜Elysia - Raytest模块开发的[镓]镓-喷替沙福合成工艺符合欧洲药典对注射用放射性药物产品的所有验收标准。发现三个GMP批次的放射化学纯度、稳定性、效力以及微生物质量良好。合成工艺的稳健性可能适用于临床环境中的多剂量应用。
