Optimized automated radiosynthesis of ¹⁸F-JNJ64413739 for purinergic ion channel receptor 7 (P2X7R) imaging in osteoporotic model rats.

IF 4.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

Frontiers in Pharmacology Pub Date : 2024-12-12 eCollection Date: 2024-01-01 DOI:10.3389/fphar.2024.1517127

Yingtong Lu, Yan Cui, Lu Hou, Yuanfang Jiang, Jingjie Shang, Lu Wang, Hao Xu, Weijian Ye, Yang Qiu, Bin Guo

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引用次数: 0

Abstract

Objective: To optimize the automated radiosynthesis of the purinergic ion channel receptor 7 (P2X7R) imaging agent ¹⁸F-JNJ64413739 and evaluate its potential for brain imaging in osteoporotic model rats.

Methods: A more electron-deficient nitropyridine was employed as the labeling precursor to facilitate the ¹⁸F-labeling. The radiosynthesis was conducted on an AllinOne synthesis module, and followed by purification via high-performance liquid chromatography (HPLC). The resulting ¹⁸F-JNJ64413739 was subjected to quality control tests. Small-animal PET/CT imaging studies were performed in sham and osteoporotic model rats.

Results: The optimized automated radiossynthesis of ¹⁸F-JNJ64413739 was successfully completed in approximately 100 min with non-decay-corrected radiochemical yield of 6.7% ± 3.8% (n = 3), >97% radiochemical purity and >14.3 ± 1.3 GBq/μmol molar activity. The product met all clinical quality requirements. ¹⁸F-JNJ64413739 PET/CT imaging showed revealed significantly higher radioactivity uptake in various brain regions of the osteoporotic model rats compared to sham control group.

Conclusion: We successfully optimized the automated radiosynthesis of ¹⁸F-JNJ64413739. The resulting tracer not only met clinical quality requirements but also demonstrated potential for clinical application in the diagnosis of osteoporosis, as evidenced by higher radioactivity uptake in various brain regions of osteoporotic model rats compared to normal controls.

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针对骨质疏松模型大鼠嘌呤能离子通道受体7 （P2X7R）成像的18F-JNJ64413739的优化自动放射合成

目的：优化嘌呤能离子通道受体7 （P2X7R）显像剂18F-JNJ64413739的自动放射合成工艺，并评价其在骨质疏松模型大鼠脑显像中的应用潜力。方法：采用更缺电子的硝基吡啶作为标记前体，促进18f标记。在AllinOne合成模块上进行放射性合成，然后通过高效液相色谱（HPLC）进行纯化。得到的18F-JNJ64413739进行了质量控制测试。对假手术大鼠和骨质疏松模型大鼠进行小动物PET/CT成像研究。结果：优化后的18F-JNJ64413739在约100 min内自动合成成功，无衰变校正的放射化学产率为6.7%±3.8% (n = 3)，放射化学纯度为>97%，放射性活性为14.3±1.3 GBq/μmol摩尔。产品符合临床质量要求。PET/CT成像显示骨质疏松模型大鼠脑各区域放射性摄取明显高于假对照组。结论：我们成功地优化了18F-JNJ64413739的自动放射合成。所制备的示踪剂不仅满足临床质量要求，而且在骨质疏松症的临床诊断中具有潜在的应用潜力，骨质疏松症模型大鼠脑各区域的放射性摄取比正常对照组高。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Pharmacology PHARMACOLOGY & PHARMACY-

CiteScore

7.80

自引率

8.90%

发文量

5163

审稿时长

14 weeks

期刊介绍： Frontiers in Pharmacology is a leading journal in its field, publishing rigorously peer-reviewed research across disciplines, including basic and clinical pharmacology, medicinal chemistry, pharmacy and toxicology. Field Chief Editor Heike Wulff at UC Davis is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.