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The expression of monocarboxylate transporters (MCTs) is linked to pathophysiological changes in diseases, including cancer, such that MCTs could potentially serve as diagnostic markers or therapeutic targets. We recently developed [ 18 F]FACH as a radiotracer for non-invasive molecular imaging of MCTs by positron emission tomography (PET). The aim of this study was to evaluate further the specificity, metabolic stability, and pharmacokinetics of [ 18 F]FACH in healthy mice and piglets. We measured the [ 18 F]FACH plasma protein binding fractions in mice and piglets and the specific binding in cryosections of murine kidney and lung. The biodistribution of [ 18 F]FACH was evaluated by tissue sampling ex vivo and by dynamic PET/MRI in vivo, with and without pre-treatment by the MCT inhibitor α-CCA-Na or the reference compound, FACH-Na. Additionally, we performed compartmental modelling of the PET signal in kidney cortex and liver. Saturation binding studies in kidney cortex cryosections indicated a K D  of 118 ± 12 nM and B max  of 6.0 pmol/mg wet weight. The specificity of [ 18 F]FACH uptake in the kidney cortex was confirmed in vivo by reductions in AUC 0-60min after pre-treatment with α-CCA-Na in mice (-47%) and in piglets (-66%). [ 18 F]FACH was metabolically stable in mouse, but polar radio-metabolites were present in plasma and tissues of piglets. The [ 18 F]FACH binding potential (BP ND ) in the kidney cortex was approximately 1.3 in mice. The MCT1 specificity of [ 18 F]FACH uptake was confirmed by displacement studies in 4T1 cells. [ 18 F]FACH has suitable properties for the detection of the MCTs in kidney, and thus has potential as a molecular imaging tool for MCT-related pathologies, which should next be assessed in relevant disease models.

Preclinical Evaluation of [18F]FACH in Healthy Mice and Piglets: An 18F-Labeled Ligand for Imaging of Monocarboxylate Transporters with PET