Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-7442
Authors: | Schieferstein, Hanno Betzel, Thomas Fischer, Cindy R. Ross, Tobias |
Title: | 18F-click labeling and preclinical evaluation of a new 18F-folate for PET imaging |
Other Title: | <sup>18</sup>F-click labeling and preclinical evaluation of a new <sup>18</sup>F-folate for PET imaging |
Online publication date: | 15-Jul-2022 |
Year of first publication: | 2013 |
Language: | english |
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 (Ki = 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. |
DDC: | 540 Chemie 540 Chemistry and allied sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 09 Chemie, Pharmazie u. Geowissensch. |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-7442 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/2.0/ |
Journal: | EJNMMI Research 3 |
Pages or article number: | Art. 68 |
Publisher: | Springer |
Publisher place: | Berlin |
Issue date: | 2013 |
ISSN: | 2191-219X |
Publisher URL: | http://dx.doi.org/10.1186/2191-219X-3-68 |
Publisher DOI: | 10.1186/2191-219X-3-68 |
Appears in collections: | DFG-OA-Publizieren (2012 - 2017) |
Files in This Item:
File | Description | Size | Format | ||
---|---|---|---|---|---|
![]() | 18fclick_labeling_and_preclin-20220714111456125.pdf | 1.3 MB | Adobe PDF | View/Open |