RESULTS:
1 - 3 of 3 for ""Tariquidar""
11C-verapamil to Assess P-gp Function in Human Brain During Aging,Depression and Neurodegenerative Disease
P-glycoprotein (P-gp) at the blood-brain barrier (BBB) functions as an active efflux pump by extruding a wide range of substrates from the brain. This is important for maintaining loco-regional homeostasis and for protecting the brain against blood-borne toxic substances. Altered P-gp function seems to be involved in the pathophysiology of neurodegenerative disease and various neurological and psychiatric disorders. Positron emission tomography (PET) with the radiotracer 11C-verapamil (VPM-PET) is a validated technique allowing measurement of P-gp function at the human BBB. In this review we highlight changes of P-gp function as measured with VPM-PET in aging and in the pathogenesis and progression of neurodegenerative disease as well as their role in depressive disorders.
Imaging of P-glycoprotein Function and Expression to Elucidate Mechanisms of Pharmacoresistance in Epilepsy
The issue of pharmacoresistance in epilepsy has received considerable attention in recent years and a number of plausible hypotheses have been proposed. Of these the so-called transporter hypothesis is the most extensively researched and documented. This hypothesis assumes that refractory epilepsy is associated with a localised over-expression of drug transporter proteins such as P-glycoprotein (Pgp) in the region of the epileptic focus which actively extrudes antiepileptic drugs (AEDs) from their intended site of action. However although this hypothesis has biological plausibility there is no clinical evidence to support the assertion that AEDs are sufficiently strong substrates for transportermediated extrusion from the brain. The use of modern brain imaging techniques to determine Pgp function in patients with refractory epilepsy has started only recently and may ultimately determine whether increased expression and function of Pgp or other efflux transporters are involved in AED resistance.
Probing Multidrug Resistance P-glycoprotein Transporter Activity with SPECT Radiopharmaceuticals
Multidrug resistance (MDR) mediated by overexpression of MDR1 (ABCB1) P-glycoprotein (Pgp) is one of the best characterized transporter-mediated barriers to successful chemotherapy in cancer patients and is also a rapidly emerging target in the progression of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Therefore molecular imaging probes capable of imaging noninvasively Pgp and closely related transporter activities in tissues as well as tumors would be expected to contribute to personalized medicine. Interrogation of Pgp-mediated transport activity in vivo via noninvasive SPECT imaging could be beneficial for stratification of patient populations likely to benefit from a given therapeutic treatment assist in the management of chemotherapy and aid the study of neurodegenerative diseases.