[C-11]quinidine and [C-11]laniquidar PET imaging in a chronic rodent epilepsy model: Impact of epilepsy and drug-responsiveness
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
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.
Positron emission tomography, [C-11]quinidine, [C-11]laniquidar, P-glycoprotein, Epilepsy
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-207645DOI: 10.1016/j.nucmedbio.2013.05.008ISI: 000323087200007OAI: oai:DiVA.org:uu-207645DiVA: diva2:649031