Brain Distribution of Dual ABCB1/ABCG2 Substrates Is Unaltered in a Beta-Amyloidosis Mouse Model
Abstract
:1. Introduction
2. Results
2.1. Immunohistochemistry
2.2. [11C]Tariquidar PET
2.3. [11C]Erlotinib PET
3. Discussion
4. Materials and Methods
4.1. General
4.2. Radiotracer Synthesis and Formulation
4.3. Animals
4.4. Experimental Design and Pretreatment
4.5. PET Imaging Procedure
4.6. PET Data Analysis
4.7. Immunohistochemistry
4.8. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ABC | Adenosine triphopshate-binding cassette |
ABCB1 | ABC subfamily B member 1, also known as P-glycoprotein (P-gp) |
ABCG2 | ABC subfamily G member 2, also known as breast cancer resistance protein (BCRP) |
AD | Alzheimer’s disease |
Aβ | Beta-amyloid |
BBB | Blood-brain barrier |
Kp,brain | Brain-to-plasma radioactivity concentration ratio |
PET | Positron Emission Tomography |
SUV | Standardized uptake value |
TAC | Time-activity curve |
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[11C]Tariquidar Study | Animal Group | ||
Pretreatment | Wild-Type | APP/PS1-21 | |
Tariquidar (12 mg/kg) and Ko143 vehicle | n | 10 (4) 1 | 7 (2) |
Age [days] 2 | 189 ± 4 | 188 ± 1 | |
Body weight [g] 2 | 26.7 ± 2.1 | 27.9 ± 3.2 | |
Injected activity [MBq] 3 | 28 ± 6 | 25 ± 3 | |
Tariquidar (12 mg/kg) and Ko143 (5 mg/kg) | n | 11 (4) | 12 (5) |
Age [days] | 181 ± 5 | 183 ± 6 | |
Body weight [g] | 28.9 ± 3.3 | 25.3 ± 2.4 | |
Injected activity [MBq] | 24 ± 7 | 23 ± 10 | |
[11C]Erlotinib Study | Animal Group | ||
Wild-Type | APP/PS1-21 | ||
n | 5 (1) | 5 (1) | |
Age [days] | 176 ± 1 | 179 ± 2 | |
Body weight [g] | 25.1 ± 1.2 | 25.2 ± 4.3 | |
Injected activity [MBq] | 19 ± 3 | 26 ± 4 |
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Wanek, T.; Zoufal, V.; Brackhan, M.; Krohn, M.; Mairinger, S.; Filip, T.; Sauberer, M.; Stanek, J.; Pekar, T.; Pahnke, J.; et al. Brain Distribution of Dual ABCB1/ABCG2 Substrates Is Unaltered in a Beta-Amyloidosis Mouse Model. Int. J. Mol. Sci. 2020, 21, 8245. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218245
Wanek T, Zoufal V, Brackhan M, Krohn M, Mairinger S, Filip T, Sauberer M, Stanek J, Pekar T, Pahnke J, et al. Brain Distribution of Dual ABCB1/ABCG2 Substrates Is Unaltered in a Beta-Amyloidosis Mouse Model. International Journal of Molecular Sciences. 2020; 21(21):8245. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218245
Chicago/Turabian StyleWanek, Thomas, Viktoria Zoufal, Mirjam Brackhan, Markus Krohn, Severin Mairinger, Thomas Filip, Michael Sauberer, Johann Stanek, Thomas Pekar, Jens Pahnke, and et al. 2020. "Brain Distribution of Dual ABCB1/ABCG2 Substrates Is Unaltered in a Beta-Amyloidosis Mouse Model" International Journal of Molecular Sciences 21, no. 21: 8245. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218245