title: Radiosynthesis and validation of (±)-[18F]-3-fluoro-2-hydroxypropionate ([18F]-FLac) as a PET tracer of lactate to monitor MCT1-dependent lactate uptake in tumors.
abstract: Cancers develop metabolic strategies to cope with their microenvironment often characterized by hypoxia, limited nutrient bioavailability and exposure to anticancer treatments. Among these strategies, the metabolic symbiosis based on the exchange of lactate between hypoxic/glycolytic cancer cells that convert glucose to lactate and oxidative cancer cells that preferentially use lactate as an oxidative fuel optimizes the bioavailability of glucose to hypoxic cancer cells. This metabolic cooperation has been described in various human cancers and can provide resistance to anti-angiogenic therapies. It depends on the expression and activity of monocarboxylate transporters (MCTs) at the cell membrane. MCT4 is the main facilitator of lactate export by glycolytic cancer cells, and MCT1 is adapted for lactate uptake by oxidative cancer cells. While MCT1 inhibitor AZD3965 is currently tested in phase I clinical trials and other inhibitors of lactate metabolism have been developed for anticancer therapy, predicting and monitoring a response to the inhibition of lactate uptake is still an unmet clinical need. Here, we report the synthesis, evaluation and in vivo validation of (±)-[18F]-3-fluoro-2-hydroxypropionate ([18F]-FLac) as a tracer of lactate for positron emission tomography. [18F]-FLac offers the possibility to monitor MCT1-dependent lactate uptake and inhibition in tumors in vivo.
authors.affiliation: Pole of Pharmacology, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCL), B-1200 Brussels, Belgium.
authors.forename: Vincent F
authors.initials: VF
authors.lastname: Van Hée
authors.affiliation: Pole of Molecular Imaging, Radiotherapy and Oncology, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCL), B-1200 Brussels, Belgium.
authors.forename: Daniel
authors.initials: D
authors.lastname: Labar
authors.affiliation: Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCL), B-1200 Brussels, Belgium.
authors.forename: Gwenaël
authors.initials: G
authors.lastname: Dehon
authors.affiliation: Pole of Pharmacology, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCL), B-1200 Brussels, Belgium.
authors.forename: Debora
authors.initials: D
authors.lastname: Grasso
authors.affiliation: Pole of Molecular Imaging, Radiotherapy and Oncology, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCL), B-1200 Brussels, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
authors.affiliation: Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCL), B-1200 Brussels, Belgium.
authors.forename: Giulio G
authors.initials: GG
authors.lastname: Muccioli
authors.affiliation: Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCL), B-1200 Brussels, Belgium.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Frédérick
authors.affiliation: Pole of Pharmacology, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCL), B-1200 Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sonveaux
mesh_terms: D049109:Cell Proliferation / Q000502:physiology; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry*; D027981:Symporters / Q000378:metabolism*; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D005462:Fluorine Radioisotopes; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D019275:Radiopharmaceuticals; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1
keywords: MCT inhibitors; cancer metabolism; metabolic symbiosis; monocarboxylate transporter 1 (MCT1); positron emission tomography (PET)