Kraihammer Martin, Garnuszek Piotr, Bauman Andreas, Maurin Michael, Alejandre Lafont Manuel, Haubner Roland, von Guggenberg Elisabeth, Gabriel Michael, Decristoforo Clemens
Department of Nuclear Medicine, Medical University Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria.
Department of Nuclear Medicine and Endocrinology, Kepler University Hospital, Linz, Austria.
EJNMMI Radiopharm Chem. 2023 Mar 27;8(1):7. doi: 10.1186/s41181-023-00191-6.
Targeted radionuclide therapy with [Lu]Lu-PSMA I&T (zadavotide guraxetan) has proven high efficacy and safety in treating patients with advanced prostate cancer worldwide. Several methods to determine the radiochemical purity have been reported but also limitations in the HPLC analysis due to retention of the sample and tailing effects when using standard gradients containing trifluoroacetic acid (TFA). We here report on the validation of a method for quality control of [Lu]Lu-PSMA I&T including determination of radiochemical purity, identity testing and limit test for PSMA I&T by HPLC using a Phosphate buffer /Acetonitrile gradient system, complemented with a TLC system with 0.1N Citrate buffer pH 5 as mobile phase including validation of the methods, batch and stability data as well as identification of the main radiochemical impurity by mass spectrometry.
The described HPLC method met the defined acceptance criteria in terms of accuracy, specificity, robustness, linearity, range and LOQ. HPLC analysis revealed symmetrical peaks and quantitative recovery from the column. Batch data showed a radiochemical purity > 95% as determined by HPLC, stability data a pronounced degradation due to radiolysis, which could be limited by addition of ascorbic acid, dilution and storage at low temperatures. The main radiochemical impurity was found to be the de-iodinated form of [Lu]Lu-PSMA I&T. TLC analysis allowed to determine the amount of free Lu-177 even in the presence of DTPA in the final formulation.
Overall the described combination of HPLC and TLC provides a reliable tool for quality control of [Lu]Lu-PSMA I&T.
[镥]镥 - PSMA I&T（扎达沃肽古拉西坦）靶向放射性核素疗法已在全球范围内证明对晚期前列腺癌患者具有高效性和安全性。已经报道了几种测定放射化学纯度的方法，但在使用含有三氟乙酸（TFA）的标准梯度时，由于样品保留和拖尾效应，HPLC分析存在局限性。我们在此报告一种用于[镥]镥 - PSMA I&T质量控制方法的验证，包括通过使用磷酸盐缓冲液/乙腈梯度系统的HPLC测定放射化学纯度、鉴别试验和PSMA I&T的限度检查，辅以以0.1N柠檬酸缓冲液pH 5为流动相的TLC系统，包括方法验证、批次和稳定性数据以及通过质谱鉴定主要放射化学杂质。
所描述的HPLC方法在准确性、特异性、稳健性、线性、范围和定量限方面符合规定的验收标准。HPLC分析显示峰形对称且从柱中定量回收。批次数据表明，通过HPLC测定放射化学纯度>95%，稳定性数据显示由于辐射分解导致明显降解，可通过添加抗坏血酸、稀释和低温储存来限制。发现主要放射化学杂质是[镥]镥 - PSMA I&T的脱碘形式。TLC分析即使在最终制剂中存在DTPA的情况下也能测定游离镥 - 177的量。
总体而言，所描述的HPLC和TLC组合为[镥]镥 - PSMA I&T的质量控制提供了可靠的工具。
