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Fluorocholine Transport Mediated by the Organic Cation Transporter 2 (OCT2, SLC22A2): Implication for Imaging of Kidney Tumors.
Visentin, Michele; Torozi, Angelo; Gai, Zhibo; Häusler, Stephanie; Li, Chao; Hiller, Christian; Schraml, Peter H; Moch, Holger; Kullak-Ublick, Gerd A.
Afiliación
  • Visentin M; Departments of Clinical Pharmacology and Toxicology (M.V., A.T., Z.G., S.H., C.L., C.H., G.A.K.-U.) and Pathology and Molecular Pathology (P.H.S., H.M.), University Hospital Zurich, University of Zurich, Zurich, Switzerland; and Shandong University of Traditional Chinese Medicine, Jinan, Shandong, C
  • Torozi A; Departments of Clinical Pharmacology and Toxicology (M.V., A.T., Z.G., S.H., C.L., C.H., G.A.K.-U.) and Pathology and Molecular Pathology (P.H.S., H.M.), University Hospital Zurich, University of Zurich, Zurich, Switzerland; and Shandong University of Traditional Chinese Medicine, Jinan, Shandong, C
  • Gai Z; Departments of Clinical Pharmacology and Toxicology (M.V., A.T., Z.G., S.H., C.L., C.H., G.A.K.-U.) and Pathology and Molecular Pathology (P.H.S., H.M.), University Hospital Zurich, University of Zurich, Zurich, Switzerland; and Shandong University of Traditional Chinese Medicine, Jinan, Shandong, C
  • Häusler S; Departments of Clinical Pharmacology and Toxicology (M.V., A.T., Z.G., S.H., C.L., C.H., G.A.K.-U.) and Pathology and Molecular Pathology (P.H.S., H.M.), University Hospital Zurich, University of Zurich, Zurich, Switzerland; and Shandong University of Traditional Chinese Medicine, Jinan, Shandong, C
  • Li C; Departments of Clinical Pharmacology and Toxicology (M.V., A.T., Z.G., S.H., C.L., C.H., G.A.K.-U.) and Pathology and Molecular Pathology (P.H.S., H.M.), University Hospital Zurich, University of Zurich, Zurich, Switzerland; and Shandong University of Traditional Chinese Medicine, Jinan, Shandong, C
  • Hiller C; Departments of Clinical Pharmacology and Toxicology (M.V., A.T., Z.G., S.H., C.L., C.H., G.A.K.-U.) and Pathology and Molecular Pathology (P.H.S., H.M.), University Hospital Zurich, University of Zurich, Zurich, Switzerland; and Shandong University of Traditional Chinese Medicine, Jinan, Shandong, C
  • Schraml PH; Departments of Clinical Pharmacology and Toxicology (M.V., A.T., Z.G., S.H., C.L., C.H., G.A.K.-U.) and Pathology and Molecular Pathology (P.H.S., H.M.), University Hospital Zurich, University of Zurich, Zurich, Switzerland; and Shandong University of Traditional Chinese Medicine, Jinan, Shandong, C
  • Moch H; Departments of Clinical Pharmacology and Toxicology (M.V., A.T., Z.G., S.H., C.L., C.H., G.A.K.-U.) and Pathology and Molecular Pathology (P.H.S., H.M.), University Hospital Zurich, University of Zurich, Zurich, Switzerland; and Shandong University of Traditional Chinese Medicine, Jinan, Shandong, C
  • Kullak-Ublick GA; Departments of Clinical Pharmacology and Toxicology (M.V., A.T., Z.G., S.H., C.L., C.H., G.A.K.-U.) and Pathology and Molecular Pathology (P.H.S., H.M.), University Hospital Zurich, University of Zurich, Zurich, Switzerland; and Shandong University of Traditional Chinese Medicine, Jinan, Shandong, C
Drug Metab Dispos ; 46(8): 1129-1136, 2018 08.
Article en En | MEDLINE | ID: mdl-29794161
ABSTRACT
[18F]fluorocholine is the fluorinated analog of [11C]choline and is used in positron emission tomography to monitor tumor metabolic activity. Although important to optimize its use and expand the clinical indications, the molecular determinants of fluorocholine cellular uptake are poorly characterized. In this work, we described the influx kinetics of fluorocholine mediated by the organic cation transporter 2 (OCT2, SLC22A2) and compared with that of choline. Then we characterized the expression pattern of OCT2 in renal cell carcinoma (RCC). In HEK293 cells stably transfected with OCT2 fluorocholine influx, kinetics was biphasic, suggesting two independent binding sites a high-affinity (Km = 14 ± 8 µM, Vmax = 1.3 ± 0.5 nmol mg-1 min-1) and a low-affinity component (Km = 1.8 ± 0.3 mM, Vmax = 104 ± 4.5 nmol mg-1 min-1). Notably, choline was found to be transported with sigmoidal kinetics typical of homotropic positive cooperativity (h = 1.2, 95% confidence interval 1.1-1.3). OCT2 mRNA expression level was found significantly decreased in primary but not in metastatic RCC. Tissue microarray immunostaining of 216 RCC biopsies confirmed that the OCT2 protein level was consistent with that of the mRNA. The kinetic properties described in this work suggest that OCT2 is likely to play a dominant role in [18F]fluorocholine uptake in vivo. OCT2-altered expression in primary and metastatic cancer cells, as compared with the surrounding tissues, could be exploited in RCC imaging, especially to increase the detection sensitivity for small metastatic lesions, a major clinical challenge during the initial staging of RCC.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Transporte Biológico / Colina / Transportador 2 de Cátion Orgánico / Riñón / Neoplasias Renales Límite: Humans Idioma: En Revista: Drug Metab Dispos Asunto de la revista: FARMACOLOGIA Año: 2018 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Transporte Biológico / Colina / Transportador 2 de Cátion Orgánico / Riñón / Neoplasias Renales Límite: Humans Idioma: En Revista: Drug Metab Dispos Asunto de la revista: FARMACOLOGIA Año: 2018 Tipo del documento: Article