Synthesis and evaluation of a 68Ga-labeled spermine derivative for tumor PET imaging

IF 3.6 4区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING Nuclear medicine and biology Pub Date : 2024-04-26 DOI:10.1016/j.nucmedbio.2024.108915

Kaixin Qin , Dongmei Shi , Yuzhou Zheng , Wenhao Hu , Xiameng Kang , Ping Wu , Xinzhong Hao , Haiyan Liu , Jie Gao , Jianguo Li , Zhifang Wu , Sijin Li , Hongliang Wang

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Abstract

Background

The polyamine transporter system (PTS), which renders it a promising target for tumor therapy and imaging applications, facilitates the transmembrane transport of polyamines. We reported a novel derivative of spermine labeled with gallium-68 ([⁶⁸Ga]Ga-NOTA-Spermine) for the imaging of the PTS in mouse models of tumor.

Results

The radiochemical yield of [⁶⁸Ga]Ga-NOTA-Spermine was determined to be 64–69 %, demonstrating exceptional stability and radiochemical purity (>98 %). Cellular uptake experiments revealed that A549 cells exhibited peak uptake of [⁶⁸Ga]Ga-NOTA-Spermine at 90 min (15.4 % ± 0.68 %). Biodistribution analysis demonstrated significant accumulation of [⁶⁸Ga]Ga-NOTA-Spermine in kidneys and liver, while exhibiting low uptake levels in muscle, brain, and bones. Furthermore, Micro-PET/CT scans conducted on A549 tumor-bearing mouse models indicated substantial uptake of [⁶⁸Ga]Ga-NOTA-Spermine, with maximum tumor/muscle (T/M) ratios reaching 3.71.

Conclusion

These results suggest that [⁶⁸Ga]Ga-NOTA-Spermine holds potential as a PET imaging agent for tumors with high levels of PTS.

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用于肿瘤 PET 成像的 68Ga 标记精胺衍生物的合成与评估

背景多胺转运体系统（PTS）促进了多胺的跨膜转运，使其成为肿瘤治疗和成像应用的一个有前途的靶点。我们报告了一种用镓-68标记的精胺衍生物（[68Ga]Ga-NOTA-Spermine），用于在小鼠肿瘤模型中对多胺转运系统进行成像。细胞摄取实验显示，A549细胞在90分钟时对[68Ga]Ga-NOTA-Spermine的摄取达到峰值（15.4 % ± 0.68 %）。生物分布分析表明，[68Ga]Ga-NOTA-Spermine在肾脏和肝脏有显著积累，而在肌肉、大脑和骨骼中的吸收水平较低。此外，对 A549 肿瘤小鼠模型进行的 Micro-PET/CT 扫描表明，[68Ga]Ga-NOTA-Spermine 被大量吸收，最大肿瘤/肌肉（T/M）比达到 3.71。

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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.