Functional imaging of multidrug resistance and its applications

Abstract

The emergence of multidrug resistance (MDR) is a major obstacle to the success of antineoplastic therapies [1]. The classical mechanism underlying MDR is the overexpression of energy-dependent transmembrane proteins behaving as drug efflux pumps. Three main proteins stand out in this family, P-glycoprotein (Pgp), multidrug resistance-associated protein-1(MRP1), and breast cancer-related protein (BCRP). Each of these transporters has the ability to confer resistance to a broad spectrum of hydrophobic chemotherapeutic agents as a result of enhanced drug efflux [2]. These pumps, in particular Pgp, have been found in several highly resistant solid and hematological tumors and are associated with a poor prognosis [3-6]. Strategies to circumvent MDR include the co-administration of modulators, compounds that inhibit the functional activity of MDR-related transporters, and the use of cytotoxic agents that bypass the efflux mechanism [7]. Information on the functional expression of MDR-related transporters has the ability to provide a rational basis for developing potentially effective therapies that can be used in patients who are likely to be poor responders to standard chemotherapy and therefore have a poor prognosis under these circumstances. © 2009 Springer-Verlag New York.