Next Article in Journal
Ouabain Contributes to Kidney Damage in a Rat Model of Renal Ischemia-Reperfusion Injury
Next Article in Special Issue
In Vivo Follow-up of Brain Tumor Growth via Bioluminescence Imaging and Fluorescence Tomography
Previous Article in Journal
Effects of Mutations on Structure–Function Relationships of Matrix Metalloproteinase-1
Previous Article in Special Issue
MALDI Mass Spectrometry Imaging Reveals Decreased CK5 Levels in Vulvar Squamous Cell Carcinomas Compared to the Precursor Lesion Differentiated Vulvar Intraepithelial Neoplasia
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(10), 1730;

Assessment of Amino Acid/Drug Transporters for Renal Transport of [18F]Fluciclovine (anti-[18F]FACBC) in Vitro

Research Center, Nihon Medi-Physics Co., Ltd., Chiba 299-0266, Japan
Wellness Promotion Science Center, Institute of Medical, Pharmaceutical and Health Science, Kanazawa University, Ishikawa 920-0942, Japan
Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, Ishikawa 920-0942, Japan
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editors: Sundaresan Gobalakrishnan and Jamal Zweit
Received: 28 July 2016 / Revised: 14 September 2016 / Accepted: 8 October 2016 / Published: 14 October 2016
(This article belongs to the Special Issue Cancer Molecular Imaging in the Era of Precision Medicine)
Full-Text   |   PDF [1484 KB, uploaded 14 October 2016]   |  


[18F]Fluciclovine (trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid; anti-[18F]FACBC), a positron emission tomography tracer used for the diagnosis of recurrent prostate cancer, is transported via amino acid transporters (AATs) with high affinity (Km: 97–230 μM). However, the mechanism underlying urinary excretion is unknown. In this study, we investigated the involvement of AATs and drug transporters in renal [18F]fluciclovine reuptake. [14C]Fluciclovine (trans-1-amino-3-fluoro[1-14C]cyclobutanecarboxylic acid) was used because of its long half-life. The involvement of AATs in [14C]fluciclovine transport was measured by apical-to-basal transport using an LLC-PK1 monolayer as model for renal proximal tubules. The contribution of drug transporters herein was assessed using vesicles/cells expressing the drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance-associated protein 4 (MRP4), organic anion transporter 1 (OAT1), organic anion transporter 3 (OAT3) , organic cation transporter 2 (OCT2), organic anion transporting polypeptide 1B1 (OATP1B1), and organic anion transporting polypeptide 1B3 (OATP1B3). The apical-to-basal transport of [14C]fluciclovine was attenuated by l-threonine, the substrate for system alanine-serine-cysteine (ASC) AATs. [14C]Fluciclovine uptake by drug transporter-expressing vesicles/cells was not significantly different from that of control vesicles/cells. Fluciclovine inhibited P-gp, MRP4, OAT1, OCT2, and OATP1B1 (IC50 > 2.95 mM). Therefore, system ASC AATs may be partly involved in the renal reuptake of [18F]fluciclovine. Further, given that [18F]fluciclovine is recognized as an inhibitor with millimolar affinity for the tested drug transporters, slow urinary excretion of [18F]fluciclovine may be mediated by system ASC AATs, but not by drug transporters. View Full-Text
Keywords: fluciclovine; anti-FACBC; positron emission tomography; amino acid transporter; drug transporter fluciclovine; anti-FACBC; positron emission tomography; amino acid transporter; drug transporter

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Ono, M.; Baden, A.; Okudaira, H.; Kobayashi, M.; Kawai, K.; Oka, S.; Yoshimura, H. Assessment of Amino Acid/Drug Transporters for Renal Transport of [18F]Fluciclovine (anti-[18F]FACBC) in Vitro. Int. J. Mol. Sci. 2016, 17, 1730.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top