P-glycoprotein (Pgp), the product of the human multidrug resistance gene (MDR1), remains a well-characterized biomarker of chemotherapeutic resistance, oral-bioavailability of drugs, and is a critical target for biomedical imaging. It is a 170 kDa plasma membrane protein, a member of the ABC (ATP-binding cassette) family of transporters, and postulated to decrease intracellular accumulation of moderately hydrophobic and cationic species. Pgp is naturally expressed in several human tissues responsible for protective and excretory functions. Importantly, emerging biochemical models of β-amyloid (Aβ) efflux pathways at the blood-brain barrier, implicate a critical role for Pgp in progression of Alzheimer’s disease and other neurodegenerative disorders. Finally, overexpression of MDR1 Pgp contributes to resistance of a broad spectrum of structurally diverse cytotoxic drugs. For interrogation of therapeutic agents likely to benefit patients undergoing chemotherapy, a noninvasive method to evaluate the functional status of P-glycoprotein activity in vivo would be desired.
Towards this goal, our lab has identified a lead agent capable of single photon emission computed tomography (SPECT)/positron emission tomography (PET) imaging for assessing MDR1 Pgp functional transport activity in vivo.