دورية أكاديمية
Cyclosporine, a P-glycoprotein modulator, increases [18F]MPPF uptake in rat brain and peripheral tissues: microPET and ex vivo studies.
| العنوان: | Cyclosporine, a P-glycoprotein modulator, increases [18F]MPPF uptake in rat brain and peripheral tissues: microPET and ex vivo studies. |
|---|---|
| المؤلفون: | Lacan, Goran, Plenevaux, Alain, Rubins, Daniel J., Way, Baldwin M., Defraiteur, Caroline, Lemaire, Christian, Aerts, Joël, Luxen, André, Cherry, Simon R., Melega, William P. |
| المساهمون: | GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège, Molecular and medical pharmacology UCLA |
| المصدر: | European Journal of Nuclear Medicine and Molecular Imaging, 35 (12), 2256-66 (2008) |
| بيانات النشر: | Springer Science & Business Media B.V. |
| سنة النشر: | 2008 |
| المجموعة: | University of Liège: ORBi (Open Repository and Bibliography) |
| مصطلحات موضوعية: | 5-HT1A receptor, positron emission tomography, hippocampus, pharmacokinetics, blood brain barrier, Human health sciences, Radiology, nuclear medicine & imaging, Sciences de la santé humaine, Radiologie, médecine & imagerie nucléaire |
| الوصف: | peer reviewed ; PURPOSE: Pretreatment with cyclosporine, a P-glycoprotein (P-gp) modulator increases brain uptake of 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethylpiperaz ine ([(18)F]MPPF) for binding to hydroxytryptamine(1A) (5-HT(1A)) receptors. Those increases were quantified in rat brain with in vivo microPET and ex vivo tissue studies. MATERIALS AND METHODS: Each Sprague-Dawley rat (n = 4) received a baseline [(18)F]MPPF microPET scan followed by second scan 2-3 weeks later that included cyclosporine pretreatment (50 mg/kg, i.p.). Maximum a posteriori reconstructed images and volumetric ROIs were used to generate dynamic radioactivity concentration measurements for hippocampus, striatum, and cerebellum, with simplified reference tissue method (SRTM) analysis. Western blots were used to semiquantify P-gp regional distribution in brain. RESULTS: MicroPET studies showed that hippocampus uptake of [(18)F]MPPF was increased after cyclosporine; ex vivo studies showed similar increases in hippocampus and frontal cortex at 30 min, and for heart and kidney at 2.5 and 5 min, without concomitant increases in [(18)F]MPPF plasma concentration. P-gp content in cerebellum was twofold higher than in hippocampus or frontal cortex. CONCLUSIONS: These studies confirm and extend prior ex vivo results (J. Passchier, et al., Eur J Pharmacol, 2000) that showed [(18)F]MPPF as a substrate for P-gp. Our microPET results showed that P-gp modulation of [(18)F]MPPF binding to 5-HT(1A) receptors can be imaged in rat hippocampus. The heterogeneous brain distribution of P-gp appeared to invalidate the use of cerebellum as a nonspecific reference region for SRTM modeling. Regional quantitation of P-gp may be necessary for accurate PET assessment of 5-HT(1A) receptor density when based on tracer uptake sensitive to P-gp modulation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1619-7070 1619-7089 |
| العلاقة: | urn:issn:1619-7070; urn:issn:1619-7089; https://orbi.uliege.be/handle/2268/5063Test; info:hdl:2268/5063; scopus-id:2-s2.0-58149301567; info:pmid:18604533 |
| DOI: | 10.1007/s00259-008-0832-z |
| الإتاحة: | https://doi.org/10.1007/s00259-008-0832-zTest https://orbi.uliege.be/handle/2268/5063Test |
| حقوق: | restricted access ; http://purl.org/coar/access_right/c_16ecTest ; info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.A13266C0 |
| قاعدة البيانات: | BASE |
| تدمد: | 16197070 16197089 |
|---|---|
| DOI: | 10.1007/s00259-008-0832-z |