Journal article
Pharmacoimaging of Blood-Brain Barrier Permeable (FDG) and Impermeable (FLT) Substrates After Intranasal (IN) Administration
The AAPS journal, Vol.20(1), 15
12/07/2017
DOI: 10.1208/s12248-017-0157-6
PMCID: PMC5798226
PMID: 29218424
Abstract
To illustrate the use of imaging to quantify the transfer of materials from the nasal cavity to other anatomical compartments, specifically, transfer to the brain using the thymidine analogue, [
F]fluorothymidine (FLT), and the glucose analogue, [
F]fluorodeoxyglucose (FDG). Anesthetized rats were administered FLT or FDG by intranasal instillation (IN) or tail-vein injection (IV). PET/CT imaging was performed for up to 60 min. Volumes-of-interest (VOIs) for the olfactory bulb (OB) and the remaining brain were created on the CT and transferred to the co-registered dynamic PET. Time-activity curves (TACs) were generated and compared. The disposition patterns were successfully visualized and quantified and differences in brain distribution patterns were observed. For FDG, the concentration was substantially higher in the OB than the brain only after IN administration. For FLT, the concentration was higher in the OB than the brain after both IN and IV and higher after IN than after IV administration at all times, whereas the concentration in the brain was higher after IN than after IV administration at early times only. Approximately 50 and 9% of the IN FDG and FLT doses, respectively, remained in the nasal cavity at 20 min post-administration. The initial phase of clearance was similar for both agents (t1/2 = 2.53 and 3.36 min) but the slow clearance phase was more rapid for FLT than FDG (t1/2 = 32.1 and 85.2 min, respectively). Pharmacoimaging techniques employing PET/CT can be successfully implemented to quantitatively investigate and compare the disposition of radiolabeled agents administered by a variety of routes.
Details
- Title: Subtitle
- Pharmacoimaging of Blood-Brain Barrier Permeable (FDG) and Impermeable (FLT) Substrates After Intranasal (IN) Administration
- Creators
- Laura L Boles Ponto - PET Imaging Center, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa, 52242, USA. laura-ponto@uiowa.eduSusan Walsh - Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAJiangeng Huang - Department of Pharmaceutics, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaChristine Mundt - PET Imaging Center, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa, 52242, USAKatherine Thede-Reynolds - PET Imaging Center, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa, 52242, USAG. Leonard Watkins - PET Imaging Center, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa, 52242, USAJohn Sunderland - PET Imaging Center, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa, 52242, USAMichael Acevedo - Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAMaureen Donovan - College of Pharmacy, Division of Pharmaceutics and Translational Therapeutics, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- The AAPS journal, Vol.20(1), 15
- DOI
- 10.1208/s12248-017-0157-6
- PMID
- 29218424
- PMCID
- PMC5798226
- NLM abbreviation
- AAPS J
- ISSN
- 1550-7416
- eISSN
- 1550-7416
- Publisher
- United States
- Grant note
- R01 DC008374 / NIDCD NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 12/07/2017
- Academic Unit
- Radiology; Pharmaceutical Sciences and Experimental Therapeutics; Physics and Astronomy; Radiation Oncology
- Record Identifier
- 9984047648702771
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