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Pharmaceutics
Volume 14
Issue 5
10.3390/pharmaceutics14051026
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Article

Indirect SPECT Imaging Evaluation for Possible Nose-to-Brain Drug Delivery Using a Compound with Poor Blood–Brain Barrier Permeability in Mice

by
Asuka Mizutani
1,†,
Masato Kobayashi
1,†,
Makoto Ohuchi
1,
Keita Sasaki
2,
Yuka Muranaka
1,
Yusuke Torikai
2,
Shota Fukakusa
2,3,
Chie Suzuki
3,
Ryuichi Nishii
4,
Shunji Haruta
2,
Yasuhiro Magata
3 and
Keiichi Kawai
1,5,*
1
Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-1192, Japan
2
R&D Department, TR Company, Shin Nippon Biomedical Laboratories, Ltd., 2438 Miyanoura, Kagoshima 891-1394, Japan
3
Department of Molecular Imaging, Institute for Medical Photonics Research, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan
4
Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan
5
Biomedical Imaging Research Center, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji, Yoshida-gun, Fukui 910-1193, Japan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Academic Editors: Frank Wuest and Leonard I. Wiebe
Pharmaceutics 2022, 14(5), 1026; https://doi.org/10.3390/pharmaceutics14051026
Received: 30 March 2022 / Revised: 22 April 2022 / Accepted: 7 May 2022 / Published: 10 May 2022
(This article belongs to the Special Issue Recent Advances in Radiopharmaceutics)
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Abstract

Single-photon emission computed tomography (SPECT) imaging using intravenous radioactive ligand administration to indirectly evaluate the time-dependent effect of intranasal drugs with poor blood-brain barrier permeability on brain drug distributions in mice was evaluated. The biodistribution was examined using domperidone, a dopamine D2 receptor ligand, as the model drug, with intranasal administration at 0, 15, or 30 min before intravenous [123I]IBZM administration. In the striatum, [123I]IBZM accumulation was significantly lower after intranasal (IN) domperidone administration than in controls 15 min after intravenous [125I]IBZM administration. [123I]IBZM SPECT was acquired with intravenous (IV) or IN domperidone administration 15 min before [123I]IBZM, and time–activity curves were obtained. In the striatum, [123I]IBZM accumulation was clearly lower in the IN group than in the control and IV groups. Time–activity curves showed no significant difference between the control and IV groups in the striatum, and values were significantly lowest during the first 10 min in the IN group. In the IN group, binding potential and % of receptor occupancy were significantly lower and higher, respectively, compared to the control and IV groups. Thus, brain-migrated domperidone inhibited D2R binding of [123I]IBZM. SPECT imaging is suitable for research to indirectly explore nose-to-brain drug delivery and locus-specific biological distribution. View Full-Text
Keywords: nose-to-brain drug delivery; poor BBB-permeable drug; brain drug distribution; dopamine D2 receptor antagonist; SPECT; [123I]IBZM nose-to-brain drug delivery; poor BBB-permeable drug; brain drug distribution; dopamine D2 receptor antagonist; SPECT; [123I]IBZM
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MDPI and ACS Style

Mizutani, A.; Kobayashi, M.; Ohuchi, M.; Sasaki, K.; Muranaka, Y.; Torikai, Y.; Fukakusa, S.; Suzuki, C.; Nishii, R.; Haruta, S.; Magata, Y.; Kawai, K. Indirect SPECT Imaging Evaluation for Possible Nose-to-Brain Drug Delivery Using a Compound with Poor Blood–Brain Barrier Permeability in Mice. Pharmaceutics 2022, 14, 1026. https://doi.org/10.3390/pharmaceutics14051026

AMA Style

Mizutani A, Kobayashi M, Ohuchi M, Sasaki K, Muranaka Y, Torikai Y, Fukakusa S, Suzuki C, Nishii R, Haruta S, Magata Y, Kawai K. Indirect SPECT Imaging Evaluation for Possible Nose-to-Brain Drug Delivery Using a Compound with Poor Blood–Brain Barrier Permeability in Mice. Pharmaceutics. 2022; 14(5):1026. https://doi.org/10.3390/pharmaceutics14051026

Chicago/Turabian Style

Mizutani, Asuka, Masato Kobayashi, Makoto Ohuchi, Keita Sasaki, Yuka Muranaka, Yusuke Torikai, Shota Fukakusa, Chie Suzuki, Ryuichi Nishii, Shunji Haruta, Yasuhiro Magata, and Keiichi Kawai. 2022. "Indirect SPECT Imaging Evaluation for Possible Nose-to-Brain Drug Delivery Using a Compound with Poor Blood–Brain Barrier Permeability in Mice" Pharmaceutics 14, no. 5: 1026. https://doi.org/10.3390/pharmaceutics14051026

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