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Open AccessArticle

Comparison Study of Two Differently Clicked 18F-Folates—Lipophilicity Plays a Key Role

1
Johannes Gutenberg-University Mainz, Institute of Nuclear Chemistry, Fritz-Straßmann-Weg 2, 55128 Mainz, Germany
2
Hannover Medical School, Department of Nuclear Medicine, Radiopharmaceutical Chemistry, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
3
University Medical Center of Johannes Gutenberg-University Mainz, Polyclinic of Nuclear Medicine, Langenbeckstr. 1, 55131 Mainz, Germany
*
Author to whom correspondence should be addressed.
The authors contributed equally.
Pharmaceuticals 2018, 11(1), 30; https://doi.org/10.3390/ph11010030
Received: 26 January 2018 / Revised: 12 March 2018 / Accepted: 14 March 2018 / Published: 17 March 2018
Within the last decade, several folate-based radiopharmaceuticals for Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) have been evaluated; however, there is still a lack of suitable 18F-folates for clinical PET imaging. Herein, we report the synthesis and evaluation of two novel 18F-folates employing strain-promoted and copper-catalyzed click chemistry. Furthermore, the influence of both click-methods on lipophilicity and pharmacokinetics of the 18F-folates was investigated. 18F-Ala-folate and 18F-DBCO-folate were both stable in human serum albumin. In vitro studies proved their high affinity to the folate receptor (FR). The lipophilic character of the strain-promoted clicked 18F-DBCO-folate (logD = 0.6) contributed to a higher non-specific binding in cell internalization studies. In the following in vivo PET imaging studies, FR-positive tumors could not be visualized in a maximum intensity projection images. Compared with 18F-DBCO-folate, 18F-Ala-folate (logD = −1.4), synthesized by the copper-catalyzed click reaction, exhibited reduced lipophilicity, and as a result an improved in vivo performance and a clear-cut visualization of FR-positive tumors. In view of high radiochemical yield, radiochemical purity and favorable pharmacokinetics, 18F-Ala-folate is expected to be a promising candidate for FR-PET imaging. View Full-Text
Keywords: 18F-folates; PET; folic acid; folate receptor; click chemistry; copper-catalyzed click; strain promoted click 18F-folates; PET; folic acid; folate receptor; click chemistry; copper-catalyzed click; strain promoted click
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MDPI and ACS Style

Kettenbach, K.; Reffert, L.M.; Schieferstein, H.; Pektor, S.; Eckert, R.; Miederer, M.; Rösch, F.; Ross, T.L. Comparison Study of Two Differently Clicked 18F-Folates—Lipophilicity Plays a Key Role. Pharmaceuticals 2018, 11, 30. https://doi.org/10.3390/ph11010030

AMA Style

Kettenbach K, Reffert LM, Schieferstein H, Pektor S, Eckert R, Miederer M, Rösch F, Ross TL. Comparison Study of Two Differently Clicked 18F-Folates—Lipophilicity Plays a Key Role. Pharmaceuticals. 2018; 11(1):30. https://doi.org/10.3390/ph11010030

Chicago/Turabian Style

Kettenbach, Kathrin; Reffert, Laura M.; Schieferstein, Hanno; Pektor, Stefanie; Eckert, Raphael; Miederer, Matthias; Rösch, Frank; Ross, Tobias L. 2018. "Comparison Study of Two Differently Clicked 18F-Folates—Lipophilicity Plays a Key Role" Pharmaceuticals 11, no. 1: 30. https://doi.org/10.3390/ph11010030

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