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 journalArticle

4 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

Keywords

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

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint Dive into the research topics of 'Development and radiosynthesis of the first <sup>18</sup>F-labeled inhibitor of monocarboxylate transporters (MCTs)'. Together they form a unique fingerprint.

  • Cite this

    Sadeghzadeh, M., Moldovan, R. P., Fischer, S., Wenzel, B., Ludwig, F. A., Teodoro, R., Deuther-Conrad, W., Jonnalagadda, S., Jonnalagadda, S. K., Gudelis, E., Šačkus, A., Higuchi, K., Ganapathy, V., Mereddy, V. R., Drewes, L. R., & Brust, P. (2019). Development and radiosynthesis of the first 18F-labeled inhibitor of monocarboxylate transporters (MCTs). Journal of Labelled Compounds and Radiopharmaceuticals, 62(8), 411-424. https://doi.org/10.1002/jlcr.3739