Pharmacoimaging of Blood-Brain Barrier Permeable (FDG) and Impermeable (FLT) Substrates After Intranasal (IN) Administration
| Autor: | Katherine Thede-Reynolds, G. Leonard Watkins, John Sunderland, Jiangeng Huang, Susan A. Walsh, Christine Mundt, Laura L. Boles Ponto, Michael R. Acevedo, Maureen D. Donovan |
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| Rok vydání: | 2017 |
| Předmět: |
Nasal cavity
Pharmaceutical Science Blood–brain barrier Permeability Article 030218 nuclear medicine & medical imaging Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Fluorodeoxyglucose F18 medicine Animals Distribution (pharmacology) Administration Intranasal Fluorodeoxyglucose Chemistry business.industry Olfactory Bulb Dideoxynucleosides Rats Olfactory bulb Nasal Absorption medicine.anatomical_structure Blood-Brain Barrier Positron-Emission Tomography 030220 oncology & carcinogenesis Initial phase Nasal administration Nasal Cavity Nuclear medicine business medicine.drug |
| Zdroj: | The AAPS Journal. 20 |
| ISSN: | 1550-7416 |
| DOI: | 10.1208/s12248-017-0157-6 |
| Popis: | 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, [18F]fluorothymidine (FLT), and the glucose analogue, [18F]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. |
| Databáze: | OpenAIRE |
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