Aalbersberg Else A, Cao Tammie T, Geluk-Jonker Martine M, Hendrikx Jeroen J M A
Department of Nuclear Medicine, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Department of Pharmacology, OLVG Locatie West, Jan Tooropstraat 164, 1061 AE, Amsterdam, The Netherlands.
EJNMMI Radiopharm Chem. 2022 Sep 27;7(1):24. doi: 10.1186/s41181-022-00178-9.
[Lu]Lu-PSMA is used for the treatment of metastatic castration-resistant prostate cancer. For in-house productions, quality control methods are essential for ensuring product quality, and thus patient safety. During HPLC method development for quality control of [Lu]Lu-PSMA-I&T, we noticed an unpredictable variability in peak area and height with replicate measurements. After a run, irremovable radioactivity was measured over the whole the length of the HPLC column, with slightly higher activity at the beginning and end of the column. The uniform distribution suggests that [Lu]Lu-PSMA-I&T interacts with the column. As a result of the interaction, incomplete and variable recovery of injected activity was observed leading to the variability in peak area and height. Therefore the aim of this study was to (1) investigate the effect of sample composition on the interaction of [Lu]Lu-PSMA-I&T to the HPLC column (measured as recovery, peak area, and peak height), and (2) to compare this with same concentrations of the well-known [Lu]Lu-PSMA-617.
Sample composition significantly affects recovery of [Lu]Lu-PSMA-I&T, leading to a change in peak area and height. Recovery was 24% when diluted with 0.1 mM octreotide, 38% with water, and increased to 95% when diluted with 0.7 mM unlabeled PSMA-I&T. Peak area and height decreased to 26% and 17% when diluted in octreotide and to 41% and 29% when diluted in water, compared to a dilution in PSMA-I&T. Further experiments showed that recovery (and consequently peak area and peak height) reached a plateau of > 99% at concentrations of 0.27 mM and higher. [Lu]Lu-PSMA-617 also interacts with the HPLC column, leading to lower, but less variable, recovery (9%). The low recovery of [Lu]Lu-PSMA-617 could not be prevented with addition of unlabeled PSMA-617.
[Lu]Lu-PSMA-I&T can undergo an irreversible binding with an HPLC column resulting in a decreased recovery. The recovery is can be highly dependent on sample composition. The addition of a surplus of unlabeled PSMA-I&T leads to an accurate analysis of [Lu]Lu-PSMA-I&T.
[镥]镥-PSMA用于治疗转移性去势抵抗性前列腺癌。对于内部生产，质量控制方法对于确保产品质量进而保障患者安全至关重要。在开发用于[镥]镥-PSMA-I&T质量控制的高效液相色谱（HPLC）方法过程中，我们注意到重复测量时峰面积和峰高存在不可预测的变化。一次运行后，在整个HPLC柱长度上均检测到不可去除的放射性，柱的起始端和末端活性略高。这种均匀分布表明[镥]镥-PSMA-I&T与柱发生了相互作用。由于这种相互作用，观察到注入活性的回收不完全且可变，导致峰面积和峰高出现变化。因此，本研究的目的是：（1）研究样品组成对[镥]镥-PSMA-I&T与HPLC柱相互作用的影响（以回收率、峰面积和峰高衡量），以及（2）将其与相同浓度的知名[镥]镥-PSMA-617进行比较。
样品组成显著影响[镥]镥-PSMA-I&T的回收率，导致峰面积和峰高发生变化。用0.1 mM奥曲肽稀释时回收率为24%，用水稀释时为38%，用0.7 mM未标记的PSMA-I&T稀释时回收率增至95%。与用PSMA-I&T稀释相比，用奥曲肽稀释时峰面积和峰高分别降至26%和17%，用水稀释时分别降至41%和29%。进一步实验表明，当浓度达到0.27 mM及更高时，回收率（进而峰面积和峰高）达到>99%的平台期。[镥]镥-PSMA-617也与HPLC柱相互作用，导致回收率较低但变化较小（9%）。添加未标记的PSMA-617无法防止[镥]镥-PSMA-617的低回收率。
[镥]镥-PSMA-I&T可与HPLC柱发生不可逆结合，导致回收率降低。回收率高度依赖于样品组成。添加过量未标记的PSMA-I&T可实现对[镥]镥-PSMA-I&T的准确分析。
