放射性薄层色谱法替代放射性高效液相色谱法用于大鼠[18F]SynVesT-1代谢分析的评价

IF 3.6 4区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Nuclear medicine and biology Pub Date : 2025-05-10 DOI:10.1016/j.nucmedbio.2025.109029

Tutukhanim Balayeva , Ruth H. Asch , Peng Wen Tan , William Mennie , Jie Tong , Baosheng Chen , Zhenwu Zhuang , Chao Zheng , MingQiang Zheng , Takuya Toyonaga , Zhengxin Cai

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引用次数: 0

摘要

突触囊泡糖蛋白2A （SV2A）的改变与各种神经退行性疾病和神经精神疾病有关。使用瞄准SV2A的放射性示踪剂（如[18F]SynVesT-1）进行正电子发射断层扫描（PET）成像，已被证明可有效监测这些变化。然而，使用动力学建模的SV2A PET定量需要放射性代谢物分析，这带来了挑战，特别是在临床前纵向研究中，由于标准的放射性高效液相色谱（radio-HPLC）方法需要相对较大的样样量。本研究旨在评价放射薄层色谱结合放射自显影（radio-TLC/AR）作为放射高效液相色谱分析大鼠血浆放射性代谢物的替代方法。方法所有大鼠静脉滴注[18F]SynVesT-1。在注射后60分钟的预定时间点采集动脉血样本。[18F]采用放射高效液相色谱法和放射薄层色谱/红外光谱法测定血浆和脑组织中的SynVesT-1放射性代谢物。结果我们观察到注射后5分钟内SynVesT-1血浆浓度[18F]下降。放射-高效液相色谱法和放射-薄层色谱/AR法得到的亲本组分显著相关(R2 = 0.99, p <；0.0001)。虽然放射性高效液相色谱在脑内检测到最小的放射性代谢物（1.34%±0.83%,n = 4），但使用放射性薄层色谱/AR方法在选定的脑区无法识别这些放射性代谢物（n = 1）。我们能够在60分钟内可靠地评估血浆中[18F]SynVesT-1的母体组分，使用正相无线电薄层色谱/AR作为无线电高效液相色谱的替代方法。这种方法需要更少的等离子体，耗时更短，重现性高。未来的研究将集中于应用这种无线电- tlc /AR方法对输入函数进行代谢校正，并利用动力学建模对PET成像数据进行定量分析。

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Evaluation of radio-thin-layer chromatography as an alternative to radio-HPLC for [18F]SynVesT-1 metabolism analysis in rats

Purpose

Alterations in synaptic vesicle glycoprotein 2A (SV2A) are linked to various neurodegenerative and neuropsychiatric disorders. Positron emission tomography (PET) imaging with radiotracers targeting SV2A, such as [¹⁸F]SynVesT-1, has proven effective for monitoring these changes. However, SV2A PET quantification using kinetic modeling requires radiometabolite analysis, which presents challenges, particularly in preclinical longitudinal studies due to the relatively large sample volume required by the standard radio-high-performance liquid chromatography (radio-HPLC) method. This study aimed to evaluate radio-thin layer chromatography combined with autoradiography (radio-TLC/AR) as an alternative to radio-HPLC in rat plasma radiometabolite analysis.

Methods

All rats received intravenous infusions of [¹⁸F]SynVesT-1. Arterial blood samples were collected at predetermined time points for up to 60 min post injection. [¹⁸F]SynVesT-1 radiometabolites in plasma and brain were assessed using both radio-HPLC and radio-TLC/AR.

Results

We observed a decline in [¹⁸F]SynVesT-1 plasma concentrations within the first 5 min post-injection. The parent fractions obtained by the radio-HPLC method significantly correlated with those obtained using radio-TLC/AR (R² = 0.99, p < 0.0001). While radio-HPLC detected minimal radiometabolites in the brain (1.34 % ± 0.83 %, n = 4), these radiometabolites were not identifiable in selected brain regions using the radio-TLC/AR method (n = 1).

Conclusion

We were able to reliably evaluate the parent fractions of [¹⁸F]SynVesT-1 in plasma over a 60-min period using normal-phase radio-TLC/AR as an alternative to radio-HPLC. This approach requires less plasma and is less time-consuming with high reproducibility. Future studies will focus on applying this radio-TLC/AR method for metabolism correction of input functions, in the quantitative analysis of PET imaging data using kinetic modeling.

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来源期刊

Nuclear medicine and biology 医学-核医学

CiteScore

6.00

自引率

9.70%

发文量

479

审稿时长

51 days

期刊介绍： Nuclear Medicine and Biology publishes original research addressing all aspects of radiopharmaceutical science: synthesis, in vitro and ex vivo studies, in vivo biodistribution by dissection or imaging, radiopharmacology, radiopharmacy, and translational clinical studies of new targeted radiotracers. The importance of the target to an unmet clinical need should be the first consideration. If the synthesis of a new radiopharmaceutical is submitted without in vitro or in vivo data, then the uniqueness of the chemistry must be emphasized. These multidisciplinary studies should validate the mechanism of localization whether the probe is based on binding to a receptor, enzyme, tumor antigen, or another well-defined target. The studies should be aimed at evaluating how the chemical and radiopharmaceutical properties affect pharmacokinetics, pharmacodynamics, or therapeutic efficacy. Ideally, the study would address the sensitivity of the probe to changes in disease or treatment, although studies validating mechanism alone are acceptable. Radiopharmacy practice, addressing the issues of preparation, automation, quality control, dispensing, and regulations applicable to qualification and administration of radiopharmaceuticals to humans, is an important aspect of the developmental process, but only if the study has a significant impact on the field. Contributions on the subject of therapeutic radiopharmaceuticals also are appropriate provided that the specificity of labeled compound localization and therapeutic effect have been addressed.