Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, Quebec, Canada; and.
Sherbrooke Molecular Imaging Center of the CRCHUS, Sherbrooke, Quebec, Canada.
J Nucl Med. 2023 Feb;64(2):232-238. doi: 10.2967/jnumed.121.263768. Epub 2022 Jul 29.
Cyclotron production of Ga is a promising approach to supply Ga radiopharmaceuticals. To validate this capability, an integrated solution for a robust synthesis of Ga-DOTATATE prepared from cyclotron-produced Ga was achieved. A retrospective comparison analysis was performed on patients who underwent PET/CT imaging after injection of DOTATATE labeled with Ga produced by a cyclotron or eluted from a generator to demonstrate the clinical safety and diagnostic efficacy of the radiopharmaceutical as a routine standard-of-care diagnostic tool in the clinic. An enriched pressed Zn target was irradiated by a cyclotron with a proton beam set at 12.7 MeV for 100 min. The fully automated process uses an in-vault dissolution system in which a liquid distribution system transfers the dissolved target to a dedicated hot cell for the purification of GaCl and radiolabeling of DOTATATE using a cassette-based automated module. Quality control tests were performed on the resulting tracer solution. The internal radiation dose for Ga-DOTATATE was based on extrapolation from rat biodistribution experiments. A retrospective comparison analysis was performed on patients who underwent PET/CT imaging after injection of DOTATATE labeled with cyclotron- or generator-produced Ga. The synthesis of Ga-DOTATATE (20.7 ± 1.3 GBq) with high apparent molar activity (518 ± 32 GBq/μmol at the end of synthesis) was completed in 65 min, and the radiopharmaceutical met the requirements specified in the monograph on Ga-chloride (accelerator-produced) solution for radiolabeling. Ga-DOTATATE was stable for at least 5 h after formulation. The dosimetry calculated with OLINDA for cyclotron- and generator-produced Ga-DOTATATE was roughly equivalent. The SUV or SUV of tumoral lesions with cyclotron-produced Ga-DOTATATE was equivalent to that with generator-produced Ga. Among physiologic uptake levels, a significant difference was found in kidneys, spleen, and stomach wall, with lower values in cyclotron-produced Ga-DOTATATE in all cases. Integrated cyclotron production achieves reliable high yields of clinical-grade Ga-DOTATATE. The clinical safety and imaging efficacy of cyclotron-produced Ga-DOTATATE in humans provide supporting evidence for its use in routine clinical practice.
回旋加速器生产的镓是供应镓放射性药物的有前途的方法。为了验证这种能力，实现了一种从回旋加速器生产的镓制备 Ga-DOTATATE 的强大合成的集成解决方案。对接受使用回旋加速器生产或从发生器洗脱的 Ga 标记的 DOTATATE 进行 PET/CT 成像的患者进行了回顾性比较分析，以证明放射性药物作为常规临床标准诊断工具的临床安全性和诊断功效。 将富集成型锌靶用 12.7 MeV 的质子束在回旋加速器中辐照 100 分钟。全自动过程使用带有内部溶解系统的地下溶解系统，该系统使用液体分配系统将溶解的靶转移到专用热室中，用于 GaCl 的纯化和使用基于盒式自动化模块的 DOTATATE 的放射性标记。对所得示踪剂溶液进行了质量控制测试。Ga-DOTATATE 的内部辐射剂量是基于大鼠生物分布实验的外推得出的。对接受使用回旋加速器或发生器生产的 Ga 标记的 DOTATATE 进行 PET/CT 成像的患者进行了回顾性比较分析。在 65 分钟内完成了高比活度（合成结束时为 518 ± 32 GBq/μmol）的 Ga-DOTATATE（20.7 ± 1.3 GBq）的合成，放射性药物符合氯化镓（加速器生产）溶液用于放射性标记的专论中规定的要求。制剂后 Ga-DOTATATE 至少稳定 5 小时。用 OLINDA 计算的回旋加速器和发生器生产的 Ga-DOTATATE 的剂量学大致相等。回旋加速器生产的 Ga-DOTATATE 与发生器生产的 Ga 的肿瘤病变的 SUV 或 SUV 相等。在生理摄取水平中，在肾脏、脾脏和胃壁中发现了显著差异，在所有情况下，回旋加速器生产的 Ga-DOTATATE 的值较低。 集成回旋加速器生产可实现可靠的高产量临床级 Ga-DOTATATE。回旋加速器生产的 Ga-DOTATATE 在人体中的临床安全性和成像功效为其在常规临床实践中的应用提供了支持证据。
