Nuclear Medicine and Molecular Imaging Department, Azienda Ospedaliero-Universitaria di Parma, via Gramsci 14, 43126Parma, Italy.
Food and Drug Sciences Department, Parco Area delle Scienze 27/A, University of Parma- 43124Parma, Italy.
Curr Radiopharm. 2021;14(2):121-130. doi: 10.2174/1874471013666200929125102.
Due to its overexpression in a variety of tumor types, the chemokine receptor 4 (CXCR4) represents a highly relevant diagnostic and therapeutic target in nuclear oncology. Recently, [Ga]Ga-DOTA-Pentixafor has emerged as an excellent imaging agent for positron emission tomography (PET) of CXCR4 expression in vivo. Preparation conditions may influence the quality and in vivo behaviour of this tracer and no standard procedure for the quality controls (QCs) is available.
The developed analytical test method was validated because a specific monograph in the Pharmacopoeia is not available for [68Ga]Ga-DOTA-Pentixafor.
A stepwise approach was used based on the quality by design (QbD) concept of the ICH Q2 (R1) and Q8 (Pharmaceutical Development) guidelines in accordance with the regulations and requirements of EANM, SNM, IAEA and WHO.
The purity and quality of the radiopharmaceutical obtained according to the proposed method were found to be high enough to safely administrate it to patients. Excellent linearity was found between 0.5 and 4 μg/mL, with a correlation coefficient (r) for calibration curves being equal to 0.999, the average coefficient of variation (CV%) < 2% and average bias% that did not deviate more than 5% for all concentrations.
This study developed a new rapid and simple HPLC method of analysis for the routine QCs of [Ga]Ga-DOTA-Pentixafor to guarantee the high quality of the finished product before release.
由于趋化因子受体 4（CXCR4）在多种肿瘤类型中过度表达，因此它是核医学中极具相关性的诊断和治疗靶标。最近，[68Ga]Ga-DOTA-Pentixafor 已成为体内 CXCR4 表达正电子发射断层扫描（PET）的优秀成像剂。制备条件可能会影响示踪剂的质量和体内行为，并且目前尚无针对该示踪剂的质量控制（QC）的标准程序。
由于[68Ga]Ga-DOTA-Pentixafor 尚无药典专论，因此开发的分析测试方法经过了验证。
根据 ICH Q2（R1）和 Q8（药物开发）指南的质量源于设计（QbD）概念，采用逐步方法，符合 EANM、SNM、IAEA 和 WHO 的规定和要求。
根据所提出的方法获得的放射性药物的纯度和质量足以安全地施用于患者。在 0.5 至 4μg/mL 之间发现了极好的线性关系，校准曲线的相关系数（r）等于 0.999，所有浓度的平均变异系数（CV%）<2%，平均偏差%不超过 5%。
本研究开发了一种新的快速简便的 HPLC 分析法，用于[68Ga]Ga-DOTA-Pentixafor 的常规 QC，以确保在放行前保证成品的高质量。
