TY - JOUR
T1 - Development and radiosynthesis of the first 18F-labeled inhibitor of monocarboxylate transporters (MCTs)
AU - Sadeghzadeh, Masoud
AU - Moldovan, Rareş Petru
AU - Fischer, Steffen
AU - Wenzel, Barbara
AU - Ludwig, Friedrich Alexander
AU - Teodoro, Rodrigo
AU - Deuther-Conrad, Winnie
AU - Jonnalagadda, Shirisha
AU - Jonnalagadda, Sravan K.
AU - Gudelis, Emilis
AU - Šačkus, Algirdas
AU - Higuchi, Kei
AU - Ganapathy, Vadivel
AU - Mereddy, Venkatram R
AU - Drewes, Lester R
AU - Brust, Peter
N1 - Publisher Copyright:
© 2019 John Wiley & Sons, Ltd.
PY - 2019/6/30
Y1 - 2019/6/30
N2 - 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%).
AB - 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%).
KW - [F]FACH
KW - monocarboxylate transporters (MCTs)
KW - positron emission tomography (PET)
KW - radiofluorination
KW - α-cyano-4-hydroxycinnamic acid (α-CHC)
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U2 - 10.1002/jlcr.3739
DO - 10.1002/jlcr.3739
M3 - Article
C2 - 31017677
AN - SCOPUS:85068929472
SN - 0362-4803
VL - 62
SP - 411
EP - 424
JO - Journal of Labelled Compounds and Radiopharmaceuticals
JF - Journal of Labelled Compounds and Radiopharmaceuticals
IS - 8
ER -