Main aims

In a multidisciplinary approach integrating radiochemistry, molecular and cellular biology, physics, pharmacology and pathology, the main aims of EURIPIDES are:

• to discover and characterise novel PET and SPET radiopharmacological tracers, which are markers for the function and the expression of cerebral multidrug transporters that form part of the BBB;
• to characterise and identify compounds / potential radiotracers in-vitro that are substrates for P-gp and acts as inhibitors of drug efflux across the BBB;
• to evaluate, determine kinetics and develop quantitative methodology to measure transporter expression and/or functionality of existing radiotracers known to be either P-gp substrates ([11C]-verapamil) or P-gp inhibitors ([11C]-laniquidar) in naïve animals (WP02, KM2.3).and in healthy human volunteers (WP05), and to later apply these methods to novel radiotracers emerging from WP01, in naïve animals (WP02) and in healthy human volunteers (WP05);
• to carry out proof-of-concept studies with existing radiotracers known to be either P-gp substrates ([11C]-VPM , [11C]-flumazenil, [18F]-MPPF) or P-gp inhibitors ([11C]-laniquidar) to image P-gp function, and determine the efficacy of existing and novel P-gp modulators to enhance cerebral penetration of substrate tracers in CNS disease models, comparing drug-resistant and drug-responsive animals (WP02, WP04) and humans (WP 04, WP05, WP06), and similarly with novel radiotracers emerging from WP01 (WP02);
• to carry out proof-of-concept studies with [11C]-verapamil to image P-gp function for early diagnosis of Alzheimer’s Disease (AD) (WP07);
• to determine the anatomical distribution of transporter proteins in brain tissue from patients with epilepsy and AD (WP08).