Synthesis and evaluation of (S)-2-(2-[18F] fluoroethoxy)-4-([3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl-carbamoyl]-methyl)-benzoic acid ([18F] repaglinide): a promising radioligand for quantification of pancreatic β-cell mass with positron emission tomography (PET)

Autoren

B Wängler
S Schneider
O Thews
E Schirrmacher
S Comagic
P Feilen
C Schwanstecher
M Schwanstecher
C-Y Shiue
A Alavi
S Höhnemann
M Piel
F Rösch
R Schirrmacher

DOI

10.1016/j.nucmedbio.2004.01.007

ISSN

0969-8051

Ausgabe der Veröffentlichung

5

Zeitschrift

Nuclear Medicine and Biology

Sprache

en

Paginierung

639 - 647

Datum der Veröffentlichung

2004

Status

Published

Herausgeber

Elsevier BV

Herausgeber URL

http://dx.doi.org/10.1016/j.nucmedbio.2004.01.007

Datum der Datenerfassung

2019

Titel

Synthesis and evaluation of (S)-2-(2-[18F]fluoroethoxy)-4-([3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl-carbamoyl]-methyl)-benzoic acid ([18F]repaglinide): a promising radioligand for quantification of pancreatic β-cell mass with positron emission tomography (PET)

Ausgabe der Zeitschrift

31

Data source: Crossref

Abstract

18F-labeled non-sulfonylurea hypoglycemic agent (S)-2-(2-[(18)F]fluoroethoxy)-4-((3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl)-methyl)-benzoic acid ([(18)F]repaglinide), a derivative of the sulfonylurea-receptor (SUR) ligand repaglinide, was synthesized as a potential tracer for the non-invasive investigation of the sulfonylurea 1 receptor status of pancreatic beta-cells by positron emission tomography (PET) in the context of type 1 and type 2 diabetes. [(18)F]Repaglinide could be obtained in an overall radiochemical yield (RCY) of 20% after 135 min with a radiochemical purity higher than 98% applying the secondary labeling precursor 2-[(18)F]fluoroethyltosylate. Specific activity was in the range of 50-60 GBq/micromol. Labeling was conducted by exchanging the ethoxy-moiety into a 2-[(18)F]fluoroethoxy group. To characterize the properties of fluorinated repaglinide, the affinity of the analogous non-radioactive (19)F-compound for binding to the human SUR1 isoform was assessed. [(19)F]Repaglinide induced a complete monophasic inhibition curve with a Hill coefficient close to 1 (1.03) yielding a dissociation constant (K(D)) of 134 nM. Biological activity was proven via insulin secretion experiments on isolated rat islets and was comparable to that of repaglinide. Finally, biodistribution of [(18)F]repaglinide was investigated in rats by measuring the concentration of the compound in different organs after i.v. injection. Pancreatic tissue displayed a stable accumulation of approximately 0.12% of the injected dose from 10 min to 30 min p.i. 50% of the radioactive tracer could be displaced by additional injection of unlabeled repaglinide, indicating that [(18)F]repaglinide might be suitable for in vivo investigation with PET.

Addresses

Institute of Nuclear Chemistry, Johannes Gutenberg-University of Mainz, Fritz Strassmann-Weg 2, D-55128 Mainz, Germany.

Autoren

B Wängler
S Schneider
O Thews
E Schirrmacher
S Comagic
P Feilen
C Schwanstecher
M Schwanstecher
C-Y Shiue
A Alavi
S Höhnemann
M Piel
F Rösch
R Schirrmacher

DOI

10.1016/j.nucmedbio.2004.01.007

eISSN

1872-9614

Externe Identifier

PubMed Identifier: 15219283

Open access

false

ISSN

0969-8051

Ausgabe der Veröffentlichung

5

Zeitschrift

Nuclear medicine and biology

Schlüsselwörter

Islets of Langerhans
Animals
Rats, Inbred Lew
Rats
Rats, Sprague-Dawley
Fluorine Radioisotopes
Carbamates
Piperidines
ATP-Binding Cassette Transporters
Multidrug Resistance-Associated Proteins
Potassium Channels, Inwardly Rectifying
Receptors, Drug
Radiopharmaceuticals
Positron-Emission Tomography
Metabolic Clearance Rate
Feasibility Studies
Isotope Labeling
Organ Specificity
Tissue Distribution
Sulfonylurea Receptors

Sprache

eng

Medium

Print

Paginierung

639 - 647

Datum der Veröffentlichung

2004

Status

Published

Datum der Datenerfassung

2004

Titel

Synthesis and evaluation of (S)-2-(2-[18F]fluoroethoxy)-4-([3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl-carbamoyl]-methyl)-benzoic acid ([18F]repaglinide): a promising radioligand for quantification of pancreatic beta-cell mass with positron emission tomography (PET).

Sub types

Comparative Study
Validation Study
Evaluation Study
Journal Article

Ausgabe der Zeitschrift

31

Data source: Europe PubMed Central

Abstract

18F-labeled non-sulfonylurea hypoglycemic agent (S)-2-(2-[(18)F]fluoroethoxy)-4-((3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl)-methyl)-benzoic acid ([(18)F]repaglinide), a derivative of the sulfonylurea-receptor (SUR) ligand repaglinide, was synthesized as a potential tracer for the non-invasive investigation of the sulfonylurea 1 receptor status of pancreatic beta-cells by positron emission tomography (PET) in the context of type 1 and type 2 diabetes. [(18)F]Repaglinide could be obtained in an overall radiochemical yield (RCY) of 20% after 135 min with a radiochemical purity higher than 98% applying the secondary labeling precursor 2-[(18)F]fluoroethyltosylate. Specific activity was in the range of 50-60 GBq/micromol. Labeling was conducted by exchanging the ethoxy-moiety into a 2-[(18)F]fluoroethoxy group. To characterize the properties of fluorinated repaglinide, the affinity of the analogous non-radioactive (19)F-compound for binding to the human SUR1 isoform was assessed. [(19)F]Repaglinide induced a complete monophasic inhibition curve with a Hill coefficient close to 1 (1.03) yielding a dissociation constant (K(D)) of 134 nM. Biological activity was proven via insulin secretion experiments on isolated rat islets and was comparable to that of repaglinide. Finally, biodistribution of [(18)F]repaglinide was investigated in rats by measuring the concentration of the compound in different organs after i.v. injection. Pancreatic tissue displayed a stable accumulation of approximately 0.12% of the injected dose from 10 min to 30 min p.i. 50% of the radioactive tracer could be displaced by additional injection of unlabeled repaglinide, indicating that [(18)F]repaglinide might be suitable for in vivo investigation with PET.

Date of acceptance

2004

Autoren

B Wängler
S Schneider
O Thews
E Schirrmacher
S Comagic
P Feilen
C Schwanstecher
M Schwanstecher
C-Y Shiue
A Alavi
S Höhnemann
M Piel
F Rösch
R Schirrmacher

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/15219283

DOI

10.1016/j.nucmedbio.2004.01.007

ISSN

0969-8051

Ausgabe der Veröffentlichung

5

Zeitschrift

Nucl Med Biol

Schlüsselwörter

ATP-Binding Cassette Transporters
Animals
Carbamates
Feasibility Studies
Fluorine Radioisotopes
Islets of Langerhans
Isotope Labeling
Metabolic Clearance Rate
Multidrug Resistance-Associated Proteins
Organ Specificity
Piperidines
Positron-Emission Tomography
Potassium Channels, Inwardly Rectifying
Radiopharmaceuticals
Rats
Rats, Inbred Lew
Rats, Sprague-Dawley
Receptors, Drug
Sulfonylurea Receptors
Tissue Distribution

Sprache

eng

Country

United States

Paginierung

639 - 647

PII

S096980510400040X

Datum der Veröffentlichung

2004

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2004

Titel

Synthesis and evaluation of (S)-2-(2-[18F]fluoroethoxy)-4-([3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl-carbamoyl]-methyl)-benzoic acid ([18F]repaglinide): a promising radioligand for quantification of pancreatic beta-cell mass with positron emission tomography (PET).

Sub types

Comparative Study
Evaluation Study
Journal Article
Validation Study

Ausgabe der Zeitschrift

31

Data source: PubMed

Autoren

B Wängler
S Schneider
O Thews
E Schirrmacher
S Comagic
P Feilen
C Schwanstecher
M Schwanstecher
C-Y Shiue
A Alavi
others

Zeitschrift

Nuclear medicine and biology

Artikelnummer

5

Paginierung

639 - 647

Datum der Veröffentlichung

2004

Herausgeber

Elsevier

Datum der Datenerfassung

2021

Titel

Synthesis and evaluation of (S)-2-(2-[18F] fluoroethoxy)-4-([3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl-carbamoyl]-methyl)-benzoic acid ([18F] repaglinide): a promising radioligand for quantification of pancreatic β-cell mass with positron emission tomography (PET)

Sub types

article

Ausgabe der Zeitschrift

31

Data source: Manual

Synthesis and evaluation of (S)-2-(2-[18F] fluoroethoxy)-4-([3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl-carbamoyl]-methyl)-benzoic acid ([18F] repaglinide): a promising radioligand for quantification of pancreatic β-cell mass with positron emission tomography (PET)

Tools