Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany.
Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany.
Nucl Med Biol. 2020 Sep-Oct;88-89:86-95. doi: 10.1016/j.nucmedbio.2020.07.008. Epub 2020 Jul 30.
[F]SiTATE (formerly known as [F]SiFAlin-TATE) was recently introduced as a highly promising imaging agent for the diagnosis of well-differentiated neuroendocrine tumors (NET) using positron emission tomography/computed tomography (PET/CT). A high tumor uptake and excellent image quality, the straightforward labeling approach, as well as the economic and logistic advantages of F- over Ga-labeled compounds predestinate [F]SiTATE to become a potential new clinical reference standard. A novel state-of-the-art methodology of automated radiopharmaceutical production is required to establish [F]SiTATE in clinical routine. This work illustrates the development of a novel synthesis procedure of [F]SiTATE on an automated synthesis unit (ASU) and the clinical applicability of the tracer in human NET imaging.
A new synthesis protocol was generated for the production of [F]SiTATE on the Scintomics GRP™ platform for clinical NET imaging. The synthesis was carried out according to common Good Manufacturing Practice (GMP) guidelines including all quality control measurements. To confirm utility, clinical batches (n = 3) were produced and applied to six patients diagnosed with NET.
[F]SiTATE was obtained in 54 ± 4% (n = 3) non-decay corrected radiochemical yield (RCY), with a radiochemical purity of 96.3 ± 0.1% and a molar activity (A) of 472 ± 45 GBq/μmol (n = 3). Quality control measurements always met the local release criteria. All specifications were taken or adapted from the Ph.Eur. regulations. PET/CT imaging with [F]SiTATE produced on the GRP™ module confirmed the expected high image quality. The in vivo distribution pattern and excellent tumor to non-tumor contrast observed, matched the quality of the manually prepared [F]SiTATE batches.
The automated manufacture of [F]SiTATE was developed using the Scintomics GRP™ platform. The high quality of the radiotracer matched stringent quality control requirements adhering to common GMP guidelines, and its clinical applicability was confirmed by human PET/CT investigations.
The automated process for the manufacture of [F]SiTATE described herein represents an important contribution to make [F]SiTATE routinely accessible for its use in clinical NET diagnosis.
[F]SiTATE（前身为[F]SiFAlin-TATE）最近被引入作为一种有前途的成像剂，用于使用正电子发射断层扫描/计算机断层扫描（PET/CT）诊断分化良好的神经内分泌肿瘤（NET）。高肿瘤摄取率和出色的图像质量、简单的标记方法以及 F-相对于 Ga 标记化合物的经济和物流优势，使[F]SiTATE 成为一种潜在的新临床参考标准。需要一种新的最先进的自动化放射性药物生产方法来将[F]SiTATE 纳入临床常规。这项工作说明了在自动化合成单元（ASU）上开发[F]SiTATE 的新合成程序以及该示踪剂在人类 NET 成像中的临床适用性。
为了在 Scintomics GRP™平台上进行临床 NET 成像，生成了一种新的[F]SiTATE 生产合成方案。合成根据常见的良好生产规范（GMP）指南进行，包括所有质量控制测量。为了确认实用性，生产了临床批次（n=3）并应用于 6 名诊断为 NET 的患者。
[F]SiTATE 的非衰变校正放射性化学产率（RCY）为 54±4%（n=3），放射性化学纯度为 96.3±0.1%，摩尔活度（A）为 472±45GBq/μmol（n=3）。质量控制测量始终符合当地放行标准。所有规格均取自或适应欧洲药典规定。使用 GRP™模块生产的[F]SiTATE 的 PET/CT 成像证实了预期的高质量图像。观察到的体内分布模式和出色的肿瘤与非肿瘤对比度与手动制备的[F]SiTATE 批次的质量相匹配。
使用 Scintomics GRP™平台开发了[F]SiTATE 的自动化生产。放射性示踪剂的高质量符合严格的质量控制要求，符合常见 GMP 指南，并通过人体 PET/CT 研究证实了其临床适用性。
本文所述的[F]SiTATE 制造自动化过程是一项重要贡献，使[F]SiTATE 能够常规用于临床 NET 诊断。
