Development and application of new 18F-labeled glycoconjugates for PET

正电子发射断层扫描(PET)被认为是临床和实验分子成像中的一种高灵敏度方法。为了更有效地使用这种方法，需要开发新的18F标记的放射性药物，这种药物可以用于患者的PET研究。考虑到2小时的短暂半衰期，18F化学的一个特别困难是复杂和耗时的放射合成。快速、可靠的标记策略的优化和高效应用是开发新型PET放射性药物的基本要求。因此，本项目的目的是利用成熟的18F-氟代糖基化方法来开发新的18F-氟代糖基化放射性配体，并对这些放射性配体进行临床前表征。这些配体旨在解决整合素avb6、前列腺特异性抗原PSMA以及雌二醇受体，从而产生用于前列腺癌、乳腺癌和胰腺肿瘤及其转移的成像的新的诊断PET放射性药物。此外，动物模型将被用来测试这些PET放射性药物以及已经建立的神经降压素受体的18F-氟糖基示踪剂是否适合于用[177Lu]Lu-Fauc 469进行神经降压素受体阳性肿瘤内放射治疗的治疗监测。选定的18F标记糖结合物的自动化和符合GMP的生产将在洁净室实验室中进行验证，长期目标是确保选定的18F-氟糖偶联物转化到临床上供患者使用。

Positron emission tomography (PET) is established as highly sensitive method in clinical and experimental molecular imaging. With the aim to use this method more efficiently, there is a need for the development of new 18F-labeled radiopharmaceuticals, which can be used in PET studies in patients. A particular difficulty of 18F-chemistry is the complex and time-consuming radiosynthesis taking into account the short half-life of 2 hours. The optimization and efficient application of fast and reliable labeling strategies are the basic requirements for the development of new PET radiopharmaceuticals. Therefore, the aim of this project is to use the well-established method of 18F-fluoroglycosylation to develop new 18F-fluoroglycosylated radioligands and to characterize these radioligands preclinically. These ligands are intended to address the integrin avb6, the prostate-specific antigen PSMA, as well as the estradiol receptor, so that new diagnostic PET radiopharmaceuticals for the imaging of prostate, breast and pancreatic tumors and their metastases arise. Furthermore, animal models will be used to test whether these PET radiopharmaceuticals, as well as an already established 18F-fluoroglycosyl tracer for the neurotensin receptor, are suitable for the therapy monitoring of endoradiotherapy of neurotensin receptor-positive tumors with [177Lu]Lu-FAUC 469. The automated and GMP-compliant production of selected 18F-labeled glycoconjugates will be validated in the clean room laboratory, with the long-term goal of ensuring the translation of the selected 18F-fluoroglycoconjugates into the clinic for patient application.