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[C-11]quinidine and...
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Syvänen, StinaUppsala universitet,Geriatrik,Rudbeck Laboratory
(author)
[C-11]quinidine and [C-11]laniquidar PET imaging in a chronic rodent epilepsy model : Impact of epilepsy and drug-responsiveness
- Article/chapterEnglish2013
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Elsevier BV,2013
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LIBRIS-ID:oai:DiVA.org:uu-207645
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-207645URI
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https://doi.org/10.1016/j.nucmedbio.2013.05.008DOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Introduction: To analyse the impact of both epilepsy and pharmacological modulation of P-glycoprotein on brain uptake and kinetics of positron emission tomography (PET) radiotracers [C-11]quinidine and [C-11]laniquidar.Methods: Metabolism and brain kinetics of both [C-11]quinidine and [C-11]laniquidar were assessed in naive rats, electrode-implanted control rats, and rats with spontaneous recurrent seizures. The latter group was further classified according to their response to the antiepileptic drug phenobarbital into "responders" and "non-responders". Additional experiments were performed following pre-treatment with the P-glycoprotein modulator tariquidar.Results: [C-11]quinidine was metabolized rapidly, whereas [C-11]laniquidar was more stable. Brain concentrations of both radiotracers remained at relatively low levels at baseline conditions. Tariquidar pre-treatment resulted in significant increases of [C-11]quinidine and [C-11]laniquidar brain concentrations. In the epileptic subgroup "non-responders", brain uptake of [C-11]quinidine in selected brain regions reached higher levels than in electrode-implanted control rats. However, the relative response to tariquidar did not differ between groups with full blockade of P-glycoprotein by 15 mg/kg of tariquidar. For [C-11]laniquidar differences between epileptic and control animals were only evident at baseline conditions but not after tariquidar pretreatment.Conclusions: We confirmed that both [C-11]quinidine and [C-11]laniquidar are P-glycoprotein substrates. At full P-gp blockade, tariquidar pre-treatment only demonstrated slight differences for [C-11]quinidine between drug-resistant and drug-sensitive animals.
Subject headings and genre
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Positron emission tomography
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[C-11]quinidine
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[C-11]laniquidar
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P-glycoprotein
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Epilepsy
Added entries (persons, corporate bodies, meetings, titles ...)
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Russmann, Vera
(author)
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Verbeek, Joost
(author)
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Eriksson, JonasDepartment of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, The Netherlands(Swepub:uu)joeri542
(author)
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Labots, Maaike
(author)
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Zellinger, Christina
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Seeger, Natalie
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Schuit, Robert
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Rongen, Marissa
(author)
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van Kooij, Rolph
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Windhorst, Albert D.
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Lammertsma, Adriaan A.
(author)
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de Lange, Elizabeth C.
(author)
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Voskuyl, Rob A.
(author)
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Koepp, Matthias
(author)
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Potschka, Heidrun
(author)
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Uppsala universitetGeriatrik
(creator_code:org_t)
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In:Nuclear Medicine and Biology: Elsevier BV40:6, s. 764-7750969-80511872-9614
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Syvänen, Stina
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Russmann, Vera
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Verbeek, Joost
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Eriksson, Jonas
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Labots, Maaike
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Zellinger, Chris ...
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Seeger, Natalie
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Schuit, Robert
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Rongen, Marissa
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van Kooij, Rolph
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Windhorst, Alber ...
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Lammertsma, Adri ...
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de Lange, Elizab ...
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Voskuyl, Rob A.
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Koepp, Matthias
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Potschka, Heidru ...
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