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本文引用的文献

1
Automation of the Radiosynthesis of Six Different F-labeled radiotracers on the AllinOne.在AllinOne上对六种不同的F标记放射性示踪剂进行放射性合成的自动化操作。
EJNMMI Radiopharm Chem. 2017;1(1):15. doi: 10.1186/s41181-016-0018-0. Epub 2016 Oct 10.
2
Evaluation of two nucleophilic syntheses routes for the automated synthesis of 6-[F]fluoro-l-DOPA.用于自动合成6-[F]氟-L-多巴的两种亲核合成路线的评估。
Nucl Med Biol. 2017 Feb;45:35-42. doi: 10.1016/j.nucmedbio.2016.10.007. Epub 2016 Oct 27.
3
An improved synthesis of the radiolabeled prostate-specific membrane antigen inhibitor, [(18) F]DCFPyL.放射性标记的前列腺特异性膜抗原抑制剂[(18)F]DCFPyL的改进合成方法。
J Labelled Comp Radiopharm. 2016 Sep;59(11):439-50. doi: 10.1002/jlcr.3430. Epub 2016 Jul 29.
4
Fully automated synthesis of [(18) F]fluoro-dihydrotestosterone ([(18) F]FDHT) using the FlexLab module.使用FlexLab模块全自动合成[(18)F]氟二氢睾酮([(18)F]FDHT)。
J Labelled Comp Radiopharm. 2016 Aug;59(10):424-8. doi: 10.1002/jlcr.3417. Epub 2016 Jul 4.
5
Automated and efficient radiosynthesis of [(18)F]FLT using a low amount of precursor.使用少量前体实现[(18)F]FLT的自动化高效放射性合成。
Nucl Med Biol. 2016 Aug;43(8):520-7. doi: 10.1016/j.nucmedbio.2016.05.009. Epub 2016 May 21.
6
Imaging metabolic heterogeneity in cancer.癌症中的成像代谢异质性
Mol Cancer. 2016 Jan 6;15:4. doi: 10.1186/s12943-015-0481-3.
7
Understanding temperatures and pressures during short radiochemical reactions.了解短放射化学反应过程中的温度和压力。
Appl Radiat Isot. 2016 Feb;108:82-91. doi: 10.1016/j.apradiso.2015.12.037. Epub 2015 Dec 11.
8
Fully-automated synthesis of 16β-(18)F-fluoro-5α-dihydrotestosterone (FDHT) on the ELIXYS radiosynthesizer.在ELIXYS放射性合成仪上全自动合成16β-(18)F-氟-5α-二氢睾酮(FDHT)。
Appl Radiat Isot. 2015 Sep;103:9-14. doi: 10.1016/j.apradiso.2015.05.010. Epub 2015 May 21.
9
Cross-sectional comparison of small animal [18F]-florbetaben amyloid-PET between transgenic AD mouse models.转基因阿尔茨海默病小鼠模型之间小动物[18F] - 氟比他班淀粉样蛋白PET的横断面比较。
PLoS One. 2015 Feb 23;10(2):e0116678. doi: 10.1371/journal.pone.0116678. eCollection 2015.
10
In vivo biodistribution of no-carrier-added 6-18F-fluoro-3,4-dihydroxy-L-phenylalanine (18F-DOPA), produced by a new nucleophilic substitution approach, compared with carrier-added 18F-DOPA, prepared by conventional electrophilic substitution.无载体添加 6-[18F]-氟-3,4-二羟基-L-苯丙氨酸(18F-DOPA)的体内生物分布,通过一种新的亲核取代方法制备,与通过传统亲电取代方法制备的载体制备的 18F-DOPA 进行比较。
J Nucl Med. 2015 Jan;56(1):106-12. doi: 10.2967/jnumed.114.145730. Epub 2014 Dec 11.

利用有限资源制备多种 PET 探针:使用单个放射性合成器制备的 24 个 F 标记化合物。

Production of diverse PET probes with limited resources: 24 F-labeled compounds prepared with a single radiosynthesizer.

机构信息

Department of Molecular & Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.

Crump Institute for Molecular Imaging, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.

出版信息

Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11309-11314. doi: 10.1073/pnas.1710466114. Epub 2017 Oct 10.

DOI:10.1073/pnas.1710466114
PMID:29073049
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5664529/
Abstract

New radiolabeled probes for positron-emission tomography (PET) are providing an ever-increasing ability to answer diverse research and clinical questions and to facilitate the discovery, development, and clinical use of drugs in patient care. Despite the high equipment and facility costs to produce PET probes, many radiopharmacies and radiochemistry laboratories use a dedicated radiosynthesizer to produce each probe, even if the equipment is idle much of the time, to avoid the challenges of reconfiguring the system fluidics to switch from one probe to another. To meet growing demand, more cost-efficient approaches are being developed, such as radiosynthesizers based on disposable "cassettes," that do not require reconfiguration to switch among probes. However, most cassette-based systems make sacrifices in synthesis complexity or tolerated reaction conditions, and some do not support custom programming, thereby limiting their generality. In contrast, the design of the ELIXYS FLEX/CHEM cassette-based synthesizer supports higher temperatures and pressures than other systems while also facilitating flexible synthesis development. In this paper, the syntheses of 24 known PET probes are adapted to this system to explore the possibility of using a single radiosynthesizer and hot cell for production of a diverse array of compounds with wide-ranging synthesis requirements, alongside synthesis development efforts. Most probes were produced with yields and synthesis times comparable to literature reports, and because hardware modification was unnecessary, it was convenient to frequently switch among probes based on demand. Although our facility supplies probes for preclinical imaging, the same workflow would be applicable in a clinical setting.

摘要

新型放射性标记探针用于正电子发射断层扫描(PET),使我们能够越来越多地回答各种研究和临床问题,并促进药物的发现、开发和临床应用。尽管生产 PET 探针需要高昂的设备和设施成本,但许多放射性药物和放射化学实验室都使用专用放射性合成仪来生产每种探针,即使设备大部分时间都处于闲置状态,也是为了避免因重新配置系统流路而从一种探针切换到另一种探针所带来的挑战。为了满足不断增长的需求,正在开发更具成本效益的方法,例如基于一次性“盒式组件”的放射性合成仪,这些方法无需重新配置即可在探针之间切换。然而,大多数基于盒式组件的系统在合成复杂性或可容忍的反应条件方面做出了牺牲,有些系统不支持定制编程,从而限制了它们的通用性。相比之下,ELIXYS FLEX/CHEM 基于盒式组件的合成仪的设计支持比其他系统更高的温度和压力,同时还便于灵活的合成开发。在本文中,我们将 24 种已知的 PET 探针的合成方法适用于该系统,以探索使用单个放射性合成仪和热室生产具有广泛合成需求的各种化合物的可能性,同时进行合成开发工作。大多数探针的产率和合成时间与文献报道相当,而且由于不需要硬件修改,因此根据需求频繁切换探针非常方便。尽管我们的设施提供用于临床前成像的探针,但相同的工作流程也适用于临床环境。