Novel 18F-Labeled PET Imaging Agent FV45 Targeting the Renin-Angiotensin System

Xinyu Chen, Mitsuru Hirano, Rudolf A. Werner, Michael Decker, Takahiro Higuchi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 (AT1), which reflects the functionality of RAS. A new 18F-labeled PET tracer derived from the clinically used AT1 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 (Ki 14.6 nM) has almost equivalent binding affinity as its lead valsartan (Ki 11.8 nM) and angiotensin II (Ki 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 AT1-selective antagonist valsartan. Overall, as the first 18F-labeled PET tracer based on a derivation from clinically used drug valsartan with almost identical chemical structure, [18F]FV45 will be a new tool for assessing the RAS function by visualizing AT1 receptor distributions and providing further information regarding cardiovascular system malfunction as well as possible applications in inflammation research and cancer diagnosis.

Original languageEnglish
Pages (from-to)10460-10470
Number of pages11
JournalACS Omega
Volume3
Issue number9
DOIs
Publication statusPublished - Sep 4 2018
Externally publishedYes

Fingerprint

Valsartan
Positron emission tomography
Angiotensins
Renin
Imaging techniques
Cardiovascular system
Blood pressure
Rats
Lead
Angiotensin Type 1 Receptor
Derivatives
Angiotensin II

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Novel 18F-Labeled PET Imaging Agent FV45 Targeting the Renin-Angiotensin System. / Chen, Xinyu; Hirano, Mitsuru; Werner, Rudolf A.; Decker, Michael; Higuchi, Takahiro.

In: ACS Omega, Vol. 3, No. 9, 04.09.2018, p. 10460-10470.

Research output: Contribution to journalArticle

Chen, Xinyu ; Hirano, Mitsuru ; Werner, Rudolf A. ; Decker, Michael ; Higuchi, Takahiro. / Novel 18F-Labeled PET Imaging Agent FV45 Targeting the Renin-Angiotensin System. In: ACS Omega. 2018 ; Vol. 3, No. 9. pp. 10460-10470.
@article{952eb2d733174444837bb811e3d58bea,
title = "Novel 18F-Labeled PET Imaging Agent FV45 Targeting the Renin-Angiotensin System",
abstract = "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 (AT1), which reflects the functionality of RAS. A new 18F-labeled PET tracer derived from the clinically used AT1 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 (Ki 14.6 nM) has almost equivalent binding affinity as its lead valsartan (Ki 11.8 nM) and angiotensin II (Ki 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 AT1-selective antagonist valsartan. Overall, as the first 18F-labeled PET tracer based on a derivation from clinically used drug valsartan with almost identical chemical structure, [18F]FV45 will be a new tool for assessing the RAS function by visualizing AT1 receptor distributions and providing further information regarding cardiovascular system malfunction as well as possible applications in inflammation research and cancer diagnosis.",
author = "Xinyu Chen and Mitsuru Hirano and Werner, {Rudolf A.} and Michael Decker and Takahiro Higuchi",
year = "2018",
month = "9",
day = "4",
doi = "10.1021/acsomega.8b01885",
language = "English",
volume = "3",
pages = "10460--10470",
journal = "ACS Omega",
issn = "2470-1343",
publisher = "American Chemical Society",
number = "9",

}

TY - JOUR

T1 - Novel 18F-Labeled PET Imaging Agent FV45 Targeting the Renin-Angiotensin System

AU - Chen, Xinyu

AU - Hirano, Mitsuru

AU - Werner, Rudolf A.

AU - Decker, Michael

AU - Higuchi, Takahiro

PY - 2018/9/4

Y1 - 2018/9/4

N2 - 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 (AT1), which reflects the functionality of RAS. A new 18F-labeled PET tracer derived from the clinically used AT1 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 (Ki 14.6 nM) has almost equivalent binding affinity as its lead valsartan (Ki 11.8 nM) and angiotensin II (Ki 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 AT1-selective antagonist valsartan. Overall, as the first 18F-labeled PET tracer based on a derivation from clinically used drug valsartan with almost identical chemical structure, [18F]FV45 will be a new tool for assessing the RAS function by visualizing AT1 receptor distributions and providing further information regarding cardiovascular system malfunction as well as possible applications in inflammation research and cancer diagnosis.

AB - 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 (AT1), which reflects the functionality of RAS. A new 18F-labeled PET tracer derived from the clinically used AT1 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 (Ki 14.6 nM) has almost equivalent binding affinity as its lead valsartan (Ki 11.8 nM) and angiotensin II (Ki 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 AT1-selective antagonist valsartan. Overall, as the first 18F-labeled PET tracer based on a derivation from clinically used drug valsartan with almost identical chemical structure, [18F]FV45 will be a new tool for assessing the RAS function by visualizing AT1 receptor distributions and providing further information regarding cardiovascular system malfunction as well as possible applications in inflammation research and cancer diagnosis.

UR - http://www.scopus.com/inward/record.url?scp=85053126827&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053126827&partnerID=8YFLogxK

U2 - 10.1021/acsomega.8b01885

DO - 10.1021/acsomega.8b01885

M3 - Article

AN - SCOPUS:85053126827

VL - 3

SP - 10460

EP - 10470

JO - ACS Omega

JF - ACS Omega

SN - 2470-1343

IS - 9

ER -