Ghent University Academic Bibliography

Advanced

Effect of cyclosporin A administration on the biodistribution and multipinhole μSPECT imaging of [123-I]R91150 in rodent brain

PETER BLANCKAERT UGent, Ingrid Burvenich, Steven Staelens UGent, SYLVIE DE BRUYNE UGent, LIESELOTTE MOERMAN UGent, Leonie wyffels UGent and Filip De Vos UGent (2009) EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING. 36(3). p.446-453
abstract
Purpose P-glycoprotein (Pgp) is an efflux protein found amongst other locations in the blood–brain barrier. It is important to investigate the effect of Pgp modulation on clinically used brain tracers, because brain uptake of the tracer can be altered by blocking of the Pgp efflux transporter. The function of Pgp can be blocked with cyclosporin A. Methods We investigated the effect of cyclosporin A administration on the biodistribution of [123I]R91150 in rodents, and the effect of Pgp blocking on the quality of multipinhole μSPECT imaging with [123I]R91150. The influence of increasing doses of cyclosporin A on the brain uptake of [123I]R91150 was investigated in NMRI mice. A biodistribution study with [123I]R91150 was performed in male Sprague-Dawley rats pretreated with cyclosporin A and not pretreated. Brain uptake of [123I]R91150 after cyclosporin A injection was compared to the brain uptake in untreated animals, and a displacement study with ketanserin was performed in both groups. A multipinhole μSPECT brain imaging study was also performed using a Milabs U-SPECT-II camera in male Sprague-Dawley rats. To exclude the effect of possible metabolites, a metabolite study was also performed. Results At the highest cyclosporin A dose (50 mg/kg), a sevenfold increase in brain radioactivity concentration was observed in NMRI mice. Also, a dose-response relationship was established between the dose of cyclosporin A and the brain uptake of [123I]R91150 in mice. Compared to the control group, a five-fold increase in [123I]R91150 radioactivity concentration was observed in the brain of Sprague-Dawley rats after cyclosporin A treatment (50 mg/kg). Radioactivity concentration in the frontal cortex increased from 0.24±0.0092 to 1.58±0.097% injected dose per gram of tissue after treatment with cyclosporin A (at the 1-h time-point). Blood radioactivity concentrations did not increase to the same extent. The cortical activity was displaced by administration of ketanserin. A metabolite study confirmed that there was no increased metabolism of [123I]R91150 due to cyclosporin A. The visual quality of multipinhole μSPECT images with [123I]R91150 in Sprague-Dawley rats improved markedly after cyclosporin A pretreatment. Conclusion From the results obtained in the biodistribution studies, it can be concluded that [123I]R91150 is a substrate for Pgp in rodents. A relationship between the administered dose of cyclosporin A and the increase in [123I]R91150 brain radioactivity concentration was established. The overall quality of our multipinhole μSPECT images with [123I]R91150 in rats improved markedly after pretreatment of the animals with cyclosporin A.
Please use this url to cite or link to this publication:
author
organization
alternative title
Effect of cyclosporin A administration on the biodistribution and multipinhole mu SPECT imaging of [I-123]R91150 in rodent brain
year
type
journalArticle (original)
publication status
published
subject
keyword
[123I]R91150, 5-HT2A receptors, Cyclosporin A, P-glycoprotein
journal title
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
Eur. J. Nucl. Med. Mol. Imaging
volume
36
issue
3
pages
446 - 453
Web of Science type
Article
Web of Science id
000263489000015
JCR category
RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
JCR impact factor
4.531 (2009)
JCR rank
7/104 (2009)
JCR quartile
1 (2009)
ISSN
1619-7070
DOI
10.1007/s00259-008-0968-x
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
727267
handle
http://hdl.handle.net/1854/LU-727267
date created
2009-08-18 11:43:16
date last changed
2010-04-09 16:04:38
@article{727267,
  abstract     = {Purpose P-glycoprotein (Pgp) is an efflux protein found amongst other locations in the blood--brain barrier. It is important to investigate the effect of Pgp modulation on clinically used brain tracers, because brain uptake of the tracer can be altered by blocking of the Pgp efflux transporter. The function of Pgp can be blocked with cyclosporin A. 
Methods  We investigated the effect of cyclosporin A administration on the biodistribution of [123I]R91150 in rodents, and the effect of Pgp blocking on the quality of multipinhole \ensuremath{\mu}SPECT imaging with [123I]R91150. The influence of increasing doses of cyclosporin A on the brain uptake of [123I]R91150 was investigated in NMRI mice. A biodistribution study with [123I]R91150 was performed in male Sprague-Dawley rats pretreated with cyclosporin A and not pretreated. Brain uptake of [123I]R91150 after cyclosporin A injection was compared to the brain uptake in untreated animals, and a displacement study with ketanserin was performed in both groups. A multipinhole \ensuremath{\mu}SPECT brain imaging study was also performed using a Milabs U-SPECT-II camera in male Sprague-Dawley rats. To exclude the effect of possible metabolites, a metabolite study was also performed. 
Results  At the highest cyclosporin A dose (50 mg/kg), a sevenfold increase in brain radioactivity concentration was observed in NMRI mice. Also, a dose-response relationship was established between the dose of cyclosporin A and the brain uptake of [123I]R91150 in mice. Compared to the control group, a five-fold increase in [123I]R91150 radioactivity concentration was observed in the brain of Sprague-Dawley rats after cyclosporin A treatment (50 mg/kg). Radioactivity concentration in the frontal cortex increased from 0.24{\textpm}0.0092 to 1.58{\textpm}0.097\% injected dose per gram of tissue after treatment with cyclosporin A (at the 1-h time-point). Blood radioactivity concentrations did not increase to the same extent. The cortical activity was displaced by administration of ketanserin. A metabolite study confirmed that there was no increased metabolism of [123I]R91150 due to cyclosporin A. The visual quality of multipinhole \ensuremath{\mu}SPECT images with [123I]R91150 in Sprague-Dawley rats improved markedly after cyclosporin A pretreatment. 
Conclusion  From the results obtained in the biodistribution studies, it can be concluded that [123I]R91150 is a substrate for Pgp in rodents. A relationship between the administered dose of cyclosporin A and the increase in [123I]R91150 brain radioactivity concentration was established. The overall quality of our multipinhole \ensuremath{\mu}SPECT images with [123I]R91150 in rats improved markedly after pretreatment of the animals with cyclosporin A.},
  author       = {BLANCKAERT, PETER and Burvenich, Ingrid and Staelens, Steven and DE BRUYNE, SYLVIE and MOERMAN, LIESELOTTE and wyffels, Leonie and De Vos, Filip},
  issn         = {1619-7070},
  journal      = {EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING},
  keyword      = {[123I]R91150,5-HT2A receptors,Cyclosporin A,P-glycoprotein},
  language     = {eng},
  number       = {3},
  pages        = {446--453},
  title        = {Effect of cyclosporin A administration on the biodistribution and multipinhole \ensuremath{\mu}SPECT imaging of [123-I]R91150 in rodent brain},
  url          = {http://dx.doi.org/10.1007/s00259-008-0968-x},
  volume       = {36},
  year         = {2009},
}

Chicago
BLANCKAERT, PETER, Ingrid Burvenich, Steven Staelens, SYLVIE DE BRUYNE, LIESELOTTE MOERMAN, Leonie wyffels, and Filip De Vos. 2009. “Effect of Cyclosporin A Administration on the Biodistribution and Multipinhole μSPECT Imaging of [123-I]R91150 in Rodent Brain.” European Journal of Nuclear Medicine and Molecular Imaging 36 (3): 446–453.
APA
BLANCKAERT, P., Burvenich, I., Staelens, S., DE BRUYNE, S., MOERMAN, L., wyffels, L., & De Vos, F. (2009). Effect of cyclosporin A administration on the biodistribution and multipinhole μSPECT imaging of [123-I]R91150 in rodent brain. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 36(3), 446–453.
Vancouver
1.
BLANCKAERT P, Burvenich I, Staelens S, DE BRUYNE S, MOERMAN L, wyffels L, et al. Effect of cyclosporin A administration on the biodistribution and multipinhole μSPECT imaging of [123-I]R91150 in rodent brain. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING. 2009;36(3):446–53.
MLA
BLANCKAERT, PETER, Ingrid Burvenich, Steven Staelens, et al. “Effect of Cyclosporin A Administration on the Biodistribution and Multipinhole μSPECT Imaging of [123-I]R91150 in Rodent Brain.” EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 36.3 (2009): 446–453. Print.