Implementation of the Cu-mediated radiofluorination methods to the production of PET radiotracers for preclinical and clinical applications

许多18F标记的PET探针的巨大诊断潜力在当前的临床实践中仍然没有完全开发，这主要是由于缺乏简单有效的制备方法。使用[18 F]氟化物的过渡金属介导的放射性同位素的新兴方法的实施应有助于已知PET示踪剂的可及性，并且还能够加速开发用于临床应用的新型分子探针。这反过来将提高临床诊断的效率，并最终提高患者护理的效率。该项目的主要重点是开发简单和节省时间的程序，用于使用铜介导的放射性同位素有效制备已知和新型PET示踪剂。该项目的主要重点在于开发放射性标记方案，该方案能够有效和节省时间地生产探针，这些探针是不可能或难以使用常规放射性同位素程序合成的。我们的努力将集中在制备已知的和新的18F标记的氨基酸和TSPO配体，适用于肿瘤和神经系统疾病的可视化。放射性标记的氨基酸能够评估癌症中的高蛋白质合成速率以及在各种神经退行性疾病中失调的单胺能系统的完整性。TSPO配体又适用于与脑功能障碍密切相关的炎症过程的成像，如帕金森病、中风和亨廷顿病。重要的是，将开发符合cGMP的自动制备示踪剂的程序。将在绒毛尿囊膜模型以及合适的啮齿动物模型中对放射性示踪剂进行体外和体内评价。本项目将与R.克拉西科娃（IHB RAS;俄罗斯联邦），在放射性标记氨基酸和其他PET示踪剂的制备程序开发以及放射合成自动化方面拥有多年经验。

The great diagnostic potential of many 18F-labeled PET-probes remains incompletely exploited in current clinical practice mainly owing to the lack of simple and efficient procedures for their preparation. Implementation of emerging methods for transition metal-mediated radiofluorination using [18F]fluoride should facilitate the accessibility of known PET tracers and, furthermore, enable an accelerated development of novel molecular probes for clinical applications. This in turn will improve the efficacy of clinical diagnostics and, ultimately, patient care. The main focus of this project is to develop simple and time-saving procedures for the efficient preparation of known and novel PET-tracers using Cu-mediated radiofluorination. The main emphasis of this project lies on the development of radiolabeling protocols which enable efficient and time-saving production of probes which are impossible or difficult to synthesize using conventional radiofluorination procedures. Our efforts will be concentrated on the preparation of already known and novel 18F-labeled amino acids and TSPO ligands suitable for visualization of tumors and neurological disorders. Radiolabeled amino acids enable to assess the high protein synthesis rate in cancer as well as the integritiy of monoaminergic systems, dysregulated in various neurodegenerative diseases. TSPO ligands are in turn suitable for imaging of inflammatory processes closely related to dysfunctions of the brain like Parkinsons disease, stroke and Huntingtons disease. Importantly, cGMP-compliant procedures for the automated preparation of the tracers are to be developed. Radiotracers will be evaluated in vitro and in vivo in a chorioallantoic membrane model as well as in suitable rodent models. This project will be carried out in cooperation with Prof. R. Krasikova (IHB RAS; Russian Federation) who has many years of experience in the development of procedures for the preparation of radiolabeled amino acids and other PET-tracers as well as in automation of radiosyntheses.