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[C-11]quinidine and [C-11]laniquidar PET imaging in a chronic rodent epilepsy model: Impact of epilepsy and drug-responsiveness
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. (Rudbeck Laboratory)
Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, The Netherlands.ORCID iD: 0000-0003-0241-092X
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2013 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 40, no 6, 764-775 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2013. Vol. 40, no 6, 764-775 p.
Keyword [en]
Positron emission tomography, [C-11]quinidine, [C-11]laniquidar, P-glycoprotein, Epilepsy
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-207645DOI: 10.1016/j.nucmedbio.2013.05.008ISI: 000323087200007OAI: oai:DiVA.org:uu-207645DiVA: diva2:649031
Available from: 2013-09-17 Created: 2013-09-17 Last updated: 2015-10-02Bibliographically approved

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Syvänen, StinaEriksson, Jonas
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