Molecules, Vol. 25, Pages 2309: Development of Novel Analogs of the Monocarboxylate Transporter Ligand FACH and Biological Validation of One Potential Radiotracer for Positron Emission Tomography (PET) Imaging

Molecules, Vol. 25, Pages 2309: Development of Novel Analogs of the Monocarboxylate Transporter Ligand FACH and Biological Validation of One Potential Radiotracer for Positron Emission Tomography (PET) Imaging Molecules doi: 10.3390/molecules25102309 Authors: Masoud Sadeghzadeh Barbara Wenzel Daniel Gündel Winnie Deuther-Conrad Magali Toussaint Rareş-Petru Moldovan Steffen Fischer Friedrich-Alexander Ludwig Rodrigo Teodoro Shirisha Jonnalagadda Sravan K. Jonnalagadda Gerrit Schüürmann Venkatram R. Mereddy Lester R. Drewes Peter Brust Monocarboxylate transporters 1-4 (MCT1-4) are involved in several metabolism-related diseases, especially cancer, providing the chance to be considered as relevant targets for diagnosis and therapy. [18F]FACH was recently developed and showed very promising preclinical results as a potential positron emission tomography (PET) radiotracer for imaging of MCTs. Given that [18F]FACH did not show high blood-brain barrier permeability, the current work is aimed to investigate whether more lipophilic analogs of FACH could improve brain uptake for imaging of gliomas, while retaining binding to MCTs. The 2-fluoropyridinyl-substituted analogs 1 and 2 were synthesized and their MCT1 inhibition was estimated by [14C]lactate uptake assay on rat brain endothelial-4 (RBE4) cells. While compounds 1 and 2 showed lower MCT1 inhibitory potencies than FACH (IC50 = 11 nM) by factors of 11 and 25, respectively, 1 (IC50 = 118 nM)...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research