Migliari Silvia, Sammartano Antonino, Scarlattei Maura, Serreli Giulio, Ghetti Caterina, Cidda Carla, Baldari Giorgio, Ortenzia Ornella, Ruffini Livia
Nuclear Medicine and Molecular Imaging Department and Medical Physics Unit, University Hospital of Parma, via Gramsci 14, 43126 Parma, Italy.
ACS Omega. 2017 Oct 31;2(10):7120-7126. doi: 10.1021/acsomega.7b00677. Epub 2017 Oct 25.
: Prostate-specific membrane antigen (PSMA) has gained high attention as a useful biomarker in the imaging evaluation of prostate cancer with positron emission tomography (PET) during recent years. [Ga]-labeled Glu-urea-Lys(Ahx)-HBED-CC ([Ga]-PSMA-HBED-CC) is a novel PSMA inhibitor radiotracer which has demonstrated its suitability in detecting prostate cancer. Preparation conditions may influence the quality and in vivo behavior of this tracer, and no standard procedure for the quality control (QC) is available. The aim of this study was to develop a new rapid and simple high-pressure liquid chromatography method of analysis for the routine QCs of [Ga]-PSMA-HBED-CC to guarantee the high quality of the radiopharmaceutical product before release. : A stepwise approach was used based on the quality by design concept of the International Conference of Harmonisation Q2 (R1) and Q8 (Pharmaceutical Development) guidelines in accordance with the regulations and requirements of European Association of Nuclear Medicine, Society of Nuclear Medicine, International Atomic Energy Agency, World Health Organization, and Italian Association of Nuclear Medicine and Molecular Imaging. The developed analytical test method was validated because a specific monograph in the pharmacopoeia is not available for [Ga]-PSMA-HBED-CC. : The purity and quality of the radiopharmaceutical obtained according to the proposed method resulted high enough to safely administrate it to patients. An excellent linearity was found between 0.8 and 5 μg/mL, with a detection limit of 0.2 μg/mL. Assay imprecision (% CV) was <2%. : The developed method to assess the radiochemical and chemical purity of [Ga]-PSMA-HBED-CC is rapid, accurate, and reproducible, allowing routinely the use of this PET tracer as a diagnostic tool for imaging prostate cancer and also assuring patient safety.
近年来，前列腺特异性膜抗原（PSMA）作为正电子发射断层扫描（PET）成像评估前列腺癌的一种有用生物标志物受到了高度关注。[镓]标记的Glu-尿素-Lys（Ahx）-HBED-CC（[镓]-PSMA-HBED-CC）是一种新型的PSMA抑制剂放射性示踪剂，已证明其在检测前列腺癌方面的适用性。制备条件可能会影响这种示踪剂的质量和体内行为，并且目前尚无用于质量控制（QC）的标准程序。本研究的目的是开发一种新的快速简便的高压液相色谱分析方法，用于[镓]-PSMA-HBED-CC的常规质量控制，以确保放射性药物产品在放行前的高质量。：根据国际协调会议Q2（R1）和Q8（药物研发）指南的质量源于设计理念，采用逐步方法，符合欧洲核医学协会、核医学协会、国际原子能机构、世界卫生组织以及意大利核医学与分子成像协会的法规和要求。由于药典中没有针对[镓]-PSMA-HBED-CC的特定专论，因此对开发的分析测试方法进行了验证。：根据所提出的方法获得的放射性药物的纯度和质量足够高，可以安全地给予患者。在0.8至5μg/mL之间发现了出色的线性关系，检测限为0.2μg/mL。测定不精密度（%CV）<2%。：所开发的评估[镓]-PSMA-HBED-CC放射化学和化学纯度的方法快速、准确且可重复，允许常规使用这种PET示踪剂作为前列腺癌成像的诊断工具，并确保患者安全。
