RT Journal Article SR Electronic T1 Impact of Organic Cation Transporters (OCT-SLC22A) on Differential Diagnosis of Intrahepatic Lesions JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 166 OP 173 DO 10.1124/dmd.116.072371 VO 45 IS 2 A1 Michele Visentin A1 Belle V. van Rosmalen A1 Christian Hiller A1 Matthanja Bieze A1 Lia Hofstetter A1 Joanne Verheij A1 Gerd A. Kullak-Ublick A1 Hermann Koepsell A1 Saffire S.K.S. Phoa A1 Ikumi Tamai A1 Roelof J. Bennink A1 Thomas M. van Gulik A1 Bruno Stieger YR 2017 UL http://dmd.aspetjournals.org/content/45/2/166.abstract AB Positron emission tomography (PET) using the cationic compound [18F]fluoromethylcholine (FCH) enhances the sensitivity for noninvasive classification of hepatic tumors due to peculiar patterns of accumulation. The underlying transporters are not known. We aim to identify the carriers mediating uptake of FCH in liver and to correlate their expression pattern with PET intrahepatic signal distribution to clarify the role of membrane transporters in FCH accumulation. FCH transport was characterized in cells overexpressing organic cation transporters (OCTs). OCT mRNA levels were determined in different types of hepatic lesions and correlated with FCH PET signal intensity. Additionally, OCT1 and OCT3 protein was analyzed in a subset of patients by Western blotting. HEK293 cells overexpressing OCT1, OCT2, or OCT3 showed higher intracellular levels of FCH in comparison with wild-type cells. mRNA levels of OCT1 paralleled protein levels and were significantly downregulated in hepatocellular carcinoma (HCC), hepatocellular adenoma (HCA), and, to a lesser extent, in focal nodular hyperplasia compared with matched nontumor tissues. In three patients with HCA, the FCH PET signal intensity was reduced relative to normal liver. This correlated with the simultaneous downregulation of OCT1 and OCT3 mRNA. In another patient with HCA, lesion and surrounding tissue did not show a difference in signal, coinciding with downregulation of OCT1 and upregulation of OCT3. Therefore, OCT1 is very likely a key transporter for the accumulation of FCH in the liver. The data support the hypothesis that the varying expression levels of OCT1 and OCT3 in focal liver lesions determine FCH PET signal intensity.