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The AAPS Journal

, 20:15 | Cite as

Pharmacoimaging of Blood-Brain Barrier Permeable (FDG) and Impermeable (FLT) Substrates After Intranasal (IN) Administration

  • Laura L. Boles Ponto
  • Susan Walsh
  • Jiangeng Huang
  • Christine Mundt
  • Katherine Thede-Reynolds
  • G. Leonard Watkins
  • John Sunderland
  • Michael Acevedo
  • Maureen Donovan
Research Article Theme: Advances and Applications of In Vivo Medical Imaging in Drug Development and Regulation
Part of the following topical collections:
  1. Theme: Advances and Applications of In Vivo Medical Imaging in Drug Development and Regulation

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, [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.

KEY WORDS

Nasal absorption Preclinical pharmacokinetics Site-specific absorption pharmacoimaging [18F]fluorothymidine (FLT) [18F]fluorodeoxyglucose (FDG) 

Notes

Acknowledgments

Research reported in this publication was supported by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health under award number R01DC008374-03S1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Supplementary material

12248_2017_157_MOESM1_ESM.mp4 (288 kb)
Figure S1 Cine of 3-dimensional reconstruction of dynamic PET data after [18F]FLT intranasal administration co-registered with CT, thresholded to display skeleton of rat. The rainbow colors reflect the concentration of FLT (red>yellow>blue). Note the migration and swallowing of dose. The intensity of the signal from the dose volume visually swamps the signal of FLT in the olfactory bulb and rest of the brain. (MP4 288 kb)
12248_2017_157_MOESM2_ESM.mp4 (971 kb)
Figure S2 Cine of 3-dimensional reconstruction of dynamic PET data after [18F]FLT intranasal administration co-registered with CT, thresholded to display outer contours of the rat. The rainbow colors reflect the concentration of FLT (red>yellow>blue). Note the presence of the dose in a single nostril only and the subsequent migration and swallowing of dose. (MP4 971 kb)

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Copyright information

© American Association of Pharmaceutical Scientists 2017

Authors and Affiliations

  • Laura L. Boles Ponto
    • 1
    • 2
  • Susan Walsh
    • 1
  • Jiangeng Huang
    • 3
    • 4
  • Christine Mundt
    • 1
    • 2
  • Katherine Thede-Reynolds
    • 1
    • 2
  • G. Leonard Watkins
    • 1
    • 2
  • John Sunderland
    • 1
    • 2
  • Michael Acevedo
    • 1
  • Maureen Donovan
    • 3
  1. 1.Department of Radiology, Roy J. and Lucille A. Carver College of MedicineUniversity of IowaIowa CityUSA
  2. 2.PET Imaging CenterUniversity of Iowa Hospitals and ClinicsIowa CityUSA
  3. 3.College of Pharmacy, Division of Pharmaceutics and Translational TherapeuticsIowa CityUSA
  4. 4.Department of Pharmaceutics, School of Pharmacy, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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