Development and radiosynthesis of the first 18F-labeled inhibitor of monocarboxylate transporters (MCTs)

Masoud Sadeghzadeh, Rareş Petru Moldovan, Steffen Fischer, Barbara Wenzel, Friedrich Alexander Ludwig, Rodrigo Teodoro, Winnie Deuther-Conrad, Shirisha Jonnalagadda, Sravan K. Jonnalagadda, Emilis Gudelis, Algirdas Šačkus, Kei Higuchi, Vadivel Ganapathy, Venkatram R Mereddy, Lester R Drewes, Peter Brust

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Monocarboxylate transporters 1 and 4 (MCT1 and MCT4) are involved in tumor development and progression. Their expression levels are related to clinical disease prognosis. Accordingly, both MCTs are promising drug targets for treatment of a variety of human cancers. The noninvasive imaging of these MCTs in cancers is regarded to be advantageous for assessing MCT-mediated effects on chemotherapy and radiosensitization using specific MCT inhibitors. Herein, we describe a method for the radiosynthesis of [18F]FACH ((E)-2-cyano-3-{4-[(3-[18F]fluoropropyl)(propyl)amino]-2-methoxyphenyl}acrylic acid), as a novel radiolabeled MCT1/4 inhibitor for imaging with PET. A fluorinated analog of α-cyano-4-hydroxycinnamic acid (FACH) was synthesized, and the inhibition of MCT1 and MCT4 was measured via an L-[14C]lactate uptake assay. Radiolabeling was performed by a two-step protocol comprising the radiosynthesis of the intermediate (E)/(Z)-[18F]tert-Bu-FACH (tert-butyl (E)/(Z)-2-cyano-3-{4-[(3-[18F]fluoropropyl)(propyl)amino]-2-methoxyphenyl}acrylate) followed by deprotection of the tert-butyl group. The radiofluorination was successfully implemented using either K[18F]F-K2.2.2-carbonate or [18F]TBAF. The final deprotected product [18F]FACH was only obtained when [18F]tert-Bu-FACH was formed by the latter procedure. After optimization of the deprotection reaction, [18F]FACH was obtained in high radiochemical yields (39.6 ± 8.3%, end of bombardment (EOB) and radiochemical purity (greater than 98%).

Original languageEnglish (US)
Pages (from-to)411-424
Number of pages14
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume62
Issue number8
DOIs
StatePublished - Jun 30 2019

Bibliographical note

Funding Information:
The Alexander von Humboldt Foundation and the University of Minnesota Duluth are acknowledged for financial supports. We are thankful to Dr. Karsten Franke for providing [18F]fluoride as well as Dr. Matthias Scheunemann for his scientific supports. We also thank the staff of the Institute of Analytical Chemistry, Department of Chemistry and Mineralogy of the University of Leipzig, for recording and processing the NMR and HR‐ MS spectra.

Funding Information:
The Alexander von Humboldt Foundation and the University of Minnesota Duluth are acknowledged for financial supports. We are thankful to Dr. Karsten Franke for providing [18F]fluoride as well as Dr. Matthias Scheunemann for his scientific supports. We also thank the staff of the Institute of Analytical Chemistry, Department of Chemistry and Mineralogy of the University of Leipzig, for recording and processing the NMR and HR-MS spectra.

Publisher Copyright:
© 2019 John Wiley & Sons, Ltd.

Keywords

  • [F]FACH
  • monocarboxylate transporters (MCTs)
  • positron emission tomography (PET)
  • radiofluorination
  • α-cyano-4-hydroxycinnamic acid (α-CHC)

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