Journal article
Demonstration of Nucleoside Transporter Activity in the Nose-to-Brain Distribution of [18F]Fluorothymidine Using PET Imaging
The AAPS journal, Vol.20(1), pp.1-9
01/2018
DOI: 10.1208/s12248-017-0158-5
PMCID: PMC5814119
PMID: 29218445
Abstract
To evaluate the role of nucleoside transporters in the nose-to-brain uptake of [18F]fluorothymidine (FLT), an equilibrative nucleoside transporter (ENT1,2) and concentrative nucleoside transporter (CNT1–3) substrate, using PET to measure local tissue concentrations. Anesthetized Sprague-Dawley rats were administered FLT by intranasal (IN) instillation or tail-vein injection (IV). NBMPR (nitrobenzylmercaptopurine riboside), an ENT1 inhibitor, was administered either IN or intraperitoneally (IP). Dynamic PET imaging was performed for up to 40 min. A CT was obtained for anatomical co-registration and attenuation correction. Time-activity curves (TACs) were generated for the olfactory bulb (OB) and remaining brain, and the area-under-the-curve (AUC) for each TAC was calculated to determine the total tissue exposure of FLT. FLT concentrations were higher in the OB than in the rest of the brain following IN administration. IP administration of NBMPR resulted in increased OB and brain FLT exposure following both IN and IV administration, suggesting that NBMPR decreases the clearance rate of FLT from the brain. When FLT and NBMPR were co-administered IN, there was a decrease in the OB AUC while an increase in the brain AUC was observed. The decrease in OB exposure was likely the result of inhibition of ENT1 uptake activity in the nose-to-brain transport pathway. FLT distribution patterns show that nucleoside transporters, including ENT1, play a key role in the distribution of transporter substrates between the nasal cavity and the brain via the OB.
Details
- Title: Subtitle
- Demonstration of Nucleoside Transporter Activity in the Nose-to-Brain Distribution of [18F]Fluorothymidine Using PET Imaging
- Creators
- Laura Ponto - 0000 0004 0434 9816 grid.412584.e PET Imaging Center University of Iowa Hospitals and Clinics 200 Hawkins Drive Iowa City Iowa 52242 USAJiangeng Huang - 0000 0004 0368 7223 grid.33199.31 Department of Pharmaceutics, School of Pharmacy, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaSusan Walsh - 0000 0004 1936 8294 grid.214572.7 Roy J. and Lucille A. Carver College of Medicine, Department of Radiology University of Iowa Iowa City Iowa USAMichael Acevedo - 0000 0004 1936 8294 grid.214572.7 Roy J. and Lucille A. Carver College of Medicine, Department of Radiology University of Iowa Iowa City Iowa USAChristine Mundt - 0000 0004 0434 9816 grid.412584.e PET Imaging Center University of Iowa Hospitals and Clinics 200 Hawkins Drive Iowa City Iowa 52242 USAJohn Sunderland - 0000 0004 0434 9816 grid.412584.e PET Imaging Center University of Iowa Hospitals and Clinics 200 Hawkins Drive Iowa City Iowa 52242 USAMaureen Donovan - 0000 0004 1936 8294 grid.214572.7 College of Pharmacy, Division of Pharmaceutics and Translational Therapeutics University of Iowa Iowa City Iowa USA
- Resource Type
- Journal article
- Publication Details
- The AAPS journal, Vol.20(1), pp.1-9
- DOI
- 10.1208/s12248-017-0158-5
- PMID
- 29218445
- PMCID
- PMC5814119
- NLM abbreviation
- AAPS J
- ISSN
- 1550-7416
- eISSN
- 1550-7416
- Publisher
- Springer International Publishing; Cham
- Language
- English
- Date published
- 01/2018
- Academic Unit
- Radiology; Pharmaceutical Sciences and Experimental Therapeutics; Physics and Astronomy; Radiation Oncology
- Record Identifier
- 9984047621502771
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