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[C-11]quinidine and...
[C-11]quinidine and [C-11]laniquidar PET imaging in a chronic rodent epilepsy model : Impact of epilepsy and drug-responsiveness
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- Syvänen, Stina (author)
- Uppsala universitet,Geriatrik,Rudbeck Laboratory
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Russmann, Vera (author)
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Verbeek, Joost (author)
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- Eriksson, Jonas (author)
- Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, The Netherlands
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Labots, Maaike (author)
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Zellinger, Christina (author)
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Seeger, Natalie (author)
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Schuit, Robert (author)
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Rongen, Marissa (author)
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van Kooij, Rolph (author)
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Windhorst, Albert D. (author)
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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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(creator_code:org_t)
- Elsevier BV, 2013
- 2013
- English.
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In: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 40:6, s. 764-775
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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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.
Keyword
- Positron emission tomography
- [C-11]quinidine
- [C-11]laniquidar
- P-glycoprotein
- Epilepsy
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Syvänen, Stina
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Russmann, Vera
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Verbeek, Joost
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Eriksson, Jonas
-
Labots, Maaike
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Zellinger, Chris ...
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show more...
-
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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show less...
- Articles in the publication
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Nuclear Medicine ...
- By the university
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Uppsala University