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Novel \(^{18}\)F-labeled PET Imaging Agent FV45 targeting the Renin-Angiotensin System

Please always quote using this URN: urn:nbn:de:bvb:20-opus-167144
  • Renin–angiotensin system (RAS) plays an important role in the regulation of blood pressure and hormonal balance. Using positron emission tomography (PET) technology, it is possible to monitor the physiological and pathological distribution of angiotensin II type 1 receptors (AT\(_1\)), which reflects the functionality of RAS. A new \(^{18}\)F-labeled PET tracer derived from the clinically used AT\(_1\) antagonist valsartan showing the least possible chemical alteration from the valsartan structure has been designed and synthesized with severalRenin–angiotensin system (RAS) plays an important role in the regulation of blood pressure and hormonal balance. Using positron emission tomography (PET) technology, it is possible to monitor the physiological and pathological distribution of angiotensin II type 1 receptors (AT\(_1\)), which reflects the functionality of RAS. A new \(^{18}\)F-labeled PET tracer derived from the clinically used AT\(_1\) antagonist valsartan showing the least possible chemical alteration from the valsartan structure has been designed and synthesized with several strategies, which can be applied for the syntheses of further derivatives. Radioligand binding study showed that the cold reference FV45 (K\(_i\) 14.6 nM) has almost equivalent binding affinity as its lead valsartan (K\(_i\) 11.8 nM) and angiotensin II (K\(_i\) 1.7 nM). Successful radiolabeling of FV45 in a one-pot radiofluorination followed by the deprotection procedure with 21.8 ± 8.5% radiochemical yield and >99% radiochemical purity (n = 5) enabled a distribution study in rats and opened a path to straightforward large-scale production. A fast and clear kidney uptake could be observed, and this renal uptake could be selectively blocked by pretreatment with AT\(_1\)-selective antagonist valsartan. Overall, as the first \(^{18}\)F-labeled PET tracer based on a derivation from clinically used drug valsartan with almost identical chemical structure, [\(^{18}\)F]FV45 will be a new tool for assessing the RAS function by visualizing AT\(_i\) receptor distributions and providing further information regarding cardiovascular system malfunction as well as possible applications in inflammation research and cancer diagnosis.show moreshow less

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Metadaten
Author: Xinyu Chen, Mitsuru Hirano, Rudolf A. Werner, Michael DeckerORCiD, Takahiro Higuchi
URN:urn:nbn:de:bvb:20-opus-167144
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Nuklearmedizin
Fakultät für Chemie und Pharmazie / Institut für Pharmazie und Lebensmittelchemie
Language:English
Parent Title (English):ACS Omega
ISSN:2470-1343
Year of Completion:2018
Volume:3
Issue:9
Pagenumber:10460−10470
Source:ACS Omega, 2018, 3 (9), pp 10460–10470. DOI: 10.1021/acsomega.8b01885
DOI:https://doi.org/10.1021/acsomega.8b01885
Sonstige beteiligte Institutionen:Johns Hopkins School of Medicine
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
GND Keyword:Positronen-Emissions-Tomografie
Tag:FV45; angiotensin II type 1 receptor; positron emission tomography; renin-angiotensin system; valsartan
Release Date:2018/09/10
Note:
This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html), which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
EU-Project number / Contract (GA) number:701983
OpenAIRE:OpenAIRE
Licence (German):License LogoDeutsches Urheberrecht