P-glycoprotein (P-gp), an efflux transporter, controls the pharmacokinetics of various compounds under physiological conditions. P-gp-mediated drug efflux has been suggested as playing a role in various disorders, including multidrug-resistant cancer and medication-refractory epilepsy. However, P-gp inhibition has had, to date, little or no clinically significant effect in multidrugresistant cancer. To enhance our understanding of its in vivo function under pathophysiological conditions, substrates of P-gp have been radiolabeled and imaged using single-photon emission computed tomography (SPECT) and positron emission tomography (PET). To accurately quantify P-gp function, a radiolabeled P-gp substrate should be selective for P-gp, produce a large signal after P-gp blockade, and generate few radiometabolites that enter the target tissue. Furthermore, quantification of P-gp function via imaging requires pharmacological inhibition of P-gp, which requires knowledge of P-gp density at the target site. By meeting these criteria, imaging can elucidate the function of P-gp in various disorders and improve the efficacy of treatments.Transporters belonging to the adenosine triphosphate (ATP)-binding cassette (ABC) superfamily maintain chemical homeostasis by mediating the transport of molecules across a membrane irrespective of concentration gradient. The ABC transporters are encoded by 48 genes in the human genome and have been grouped into seven subfamilies (designated ABCA-ABCG) based on sequence homology. 1,2 These genes encode membrane proteins with a range of subcellular localizations and substrate specificities. Of these transporter genes, ABCB1 has been most studied because it encodes P-glycoprotein ((P-gp) or multidrug resistance 1 (MDR1)), a 170-kDa lipoprotein widely expressed in plasma cell membranes of healthy human tissues and multidrug-resistant tumors. 1,2 STRUCTURAL AND FUNCTIONAL CHARACTERISTICS OF P-GPThe structural and functional characteristics of P-gp help explain its role under both physiological and pathophyiological conditions. 3 Structurally, the transporter consists of two Correspondence: RB Innis (robert.innis@nih.gov). CONFLICT OF INTERESTThe authors declared no conflict of interest. NIH Public Access Author ManuscriptClin Pharmacol Ther. Author manuscript; available in PMC 2009 October 1. Published in final edited form as:Clin Pharmacol Ther. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript interwoven transmembrane regions, each containing six transmembrane helices and an ATPbinding site located intracellularly (Figure 1 and refs. 1,4,5 ). The transmembrane helices of Pgp allow it to bind and induce efflux of a broad range of substrates with varying affinities. Functionally, P-gp regulates the transport of biologically important molecules, nutrients, hormones, and xenobiotics into and/or out of cells. 3 Although substrates for P-gp tend to be hydrophobic or weak base molecules with a planar ring system, 6 P-gp is considered polyspecific because it can recogni...

Gemtuzumab ozogamicin (GO) 3 mg/m days 1, 4, and 7 is an active regimen for induction of remission when used to treat patients with relapsed or refractory CD33-positive acute myeloid leukemia without curative intent. The risks of hepatic veno-occlusive disease and early mortality with this regimen appear to be lower than reported previously for GO 9 mg/m days 1 and 15. The data were not sufficient to enable conclusions about the safety of GO in children younger than 2 years of age.

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