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Open Access 01-12-2013 | Original research

¹⁸ F-click labeling and preclinical evaluation of a new ¹⁸ F-folate for PET imaging

Authors: Hanno Schieferstein, Thomas Betzel, Cindy R Fischer, Tobias L Ross

Published in: EJNMMI Research | Issue 1/2013

Abstract

Background

The folate receptor (FR) is a well-established target for tumor imaging and therapy. To date, only a few ¹⁸ F-folate conjugates via ¹⁸ F-prosthetic group labeling for positron emission tomography (PET) imaging have been developed. To some extent, they all lack the optimal balance between efficient radiochemistry and favorable in vivo characteristics.

Methods

A new clickable olate precursor was synthesized by regioselective coupling of folic acid to 11-azido-3,6,9-trioxaundecan-1-amine at the γ-position of the glutamic acid residue. The non-radioactive reference compound was synthesized via copper-catalyzed azide-alkyne cycloaddition of 3-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)prop-1-yne and γ-(11-azido-3,6,9-trioxaundecanyl)folic acid amide. The radiosynthesis was accomplished in two steps: at first a ¹⁸ F-fluorination of 2-(2-(2-(prop-2-yn-1-yloxy)ethoxy)ethoxy)ethyl-4-methylbenzenesulfonate, followed by a ¹⁸ F-click reaction with the γ-azido folate. The in vitro, ex vivo, and in vivo behaviors of the new ¹⁸ F-folate were investigated using FR-positive human KB cells in displacement assays and microPET studies using KB tumor-bearing mice.

Results

The new ¹⁸ F-folate with oligoethylene spacers showed reduced lipophilicity in respect to the previously developed ¹⁸ F-click folate with alkyl spacers and excellent affinity (K _i = 1.6 nM) to the FR. Combining the highly efficient ¹⁸ F-click chemistry and a polar oligoethylene-based ¹⁸ F-prosthetic group facilitated these results. The overall radiochemical yield of the isolated and formulated product averages 8.7%. In vivo PET imaging in KB tumor-bearing mice showed a tumor uptake of 3.4% ID/g tissue, which could be reduced by FR blockade with native folic acid. Although the new ¹⁸ F-oligoethyleneglycole (OEG)-folate showed reduced hepatobiliary excretion over time, a distinct unspecific abdominal background was still observed.

Conclusions

A new ¹⁸ F-folate was developed, being available in very high radiochemical yields via a fast and convenient two-step radiosynthesis. The new ¹⁸ F-OEG-folate showed good in vivo behavior and lines up with several recently evaluated ¹⁸ F-labeled folates.

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Title: 18 F-click labeling and preclinical evaluation of a new 18 F-folate for PET imaging
Authors: Hanno Schieferstein
Thomas Betzel
Cindy R Fischer
Tobias L Ross
Publication date: 01-12-2013
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2013
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/2191-219X-3-68

Keynote webinar | Spotlight on medication adherence

Springer Medicine

¹⁸ F-click labeling and preclinical evaluation of a new ¹⁸ F-folate for PET imaging

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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