一种快速且特异的 HPLC 方法，用于测定 [Ga]Ga-DOTA-Pentixafor（PET 示踪剂）的化学纯度和放射化学纯度：开发与验证。

A Rapid and Specific HPLC Method to Determine Chemical and Radiochemical Purity of [Ga]Ga-DOTA-Pentixafor (PET) Tracer: Development and Validation.

机构信息

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.

出版信息

Curr Radiopharm. 2021;14(2):121-130. doi: 10.2174/1874471013666200929125102.

DOI:10.2174/1874471013666200929125102

PMID:32990551

Abstract

BACKGROUND

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.

OBJECTIVE

The developed analytical test method was validated because a specific monograph in the Pharmacopoeia is not available for [68Ga]Ga-DOTA-Pentixafor.

METHOD

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。