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

1 Citation (Scopus)

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

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Imaging techniques
Neoplasms
Chemotherapy
Carbonates
4-coumaric acid
Tumors
Lactic Acid
Assays
Drug Therapy
Pharmaceutical Preparations
acrylic acid
Therapeutics

Keywords

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

PubMed: MeSH publication types

  • Journal Article

Cite this

Sadeghzadeh, M., Moldovan, R. P., Fischer, S., Wenzel, B., Ludwig, F. A., Teodoro, 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

Development and radiosynthesis of the first 18F-labeled inhibitor of monocarboxylate transporters (MCTs). / Sadeghzadeh, Masoud; Moldovan, Rareş Petru; Fischer, Steffen; Wenzel, Barbara; Ludwig, Friedrich Alexander; Teodoro, Rodrigo; Deuther-Conrad, Winnie; Jonnalagadda, Shirisha; Jonnalagadda, Sravan K.; Gudelis, Emilis; Šačkus, Algirdas; Higuchi, Kei; Ganapathy, Vadivel; Mereddy, Venkatram R; Drewes, Lester R; Brust, Peter.

In: Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 62, No. 8, 30.06.2019, p. 411-424.

Research output: Contribution to journalArticle

Sadeghzadeh, M, Moldovan, RP, Fischer, S, Wenzel, B, Ludwig, FA, Teodoro, R, Deuther-Conrad, W, Jonnalagadda, S, Jonnalagadda, SK, Gudelis, E, Šačkus, A, Higuchi, K, Ganapathy, V, Mereddy, VR, Drewes, LR & Brust, P 2019, 'Development and radiosynthesis of the first 18F-labeled inhibitor of monocarboxylate transporters (MCTs)', Journal of Labelled Compounds and Radiopharmaceuticals, vol. 62, no. 8, pp. 411-424. https://doi.org/10.1002/jlcr.3739
Sadeghzadeh, Masoud ; Moldovan, Rareş Petru ; Fischer, Steffen ; Wenzel, Barbara ; Ludwig, Friedrich Alexander ; Teodoro, Rodrigo ; Deuther-Conrad, Winnie ; Jonnalagadda, Shirisha ; Jonnalagadda, Sravan K. ; Gudelis, Emilis ; Šačkus, Algirdas ; Higuchi, Kei ; Ganapathy, Vadivel ; Mereddy, Venkatram R ; Drewes, Lester R ; Brust, Peter. / Development and radiosynthesis of the first 18F-labeled inhibitor of monocarboxylate transporters (MCTs). In: Journal of Labelled Compounds and Radiopharmaceuticals. 2019 ; Vol. 62, No. 8. pp. 411-424.
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AU - Ludwig, Friedrich Alexander

AU - Teodoro, Rodrigo

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