RT Journal Article SR Electronic T1 Evaluation of P-glycoprotein function using microPET and 11C-dLop in rats JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1199 OP 1199 VO 50 IS supplement 2 A1 Yasuhiko Iida A1 Derek Chong A1 Michael Farwell A1 Balu Easwaramoorthy A1 Sung Bae A1 Chitra Saxena A1 Dileep Kumar A1 Ronald Van Heertum A1 Frank Giliam A1 Masanori Ichise YR 2009 UL http://jnm.snmjournals.org/content/50/supplement_2/1199.abstract AB 1199 Objectives Drug resistance is a problem in the treatment of various diseases, such as epilepsy. One of mechanisms responsible for this resistance may be up-regulation of P-glycoprotein (P-gp) drug efflux pump. In this rat brain study, we sought to evaluate the potential of newly developed P-gp PET tracer, 11C-N-desmethyl-loperamide 11C-dLop), for measuring P-gp function. Methods 11C-dLop was synthesized as described previously (J. Med. Chem. 2008, 51, 6034-6043). We studied two groups of rats, controls (n=4) and inhibitors (n=5), with cyclosporine A (CsA), 50mg/kg, or tariquidar (TQ), 20mg/kg. MicroPET brain scans were performed for 120min with arterial blood sampling. One-tissue compartment model was used to estimate the distribution volume (VT) of radiotracer as the outcome measure of P-gp function. Results Parent 11C-dLop in plasma rapidly decreased to <0.1 SUV at 60min. In controls, brain uptake of 11C-dLop was very low <0.1 SUV. In contrast, the SUVs were significantly higher in CsA (0.51) and TQ (0.22). A 70min scan was sufficient to obtain stable VT (control=2.1, CsA=7.3, TQ=4.7), showing significant effects of P-gp inhibition. Conclusions 11C-dLop is a substrate for P-gp and shows very low brain uptake without P-gp inhibition, but with inhibition, there is a significant rise in the tracer brain uptake. 11C-dLop is a promising radiotracer to study the P-gp function.