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Leung K.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2005 Dec 20 [updated 2012 Feb 07].


One of the mechanisms by which cells mitigate the cytotoxic effects of chemotherapeutic agents, such as Adriamycin, Vinca alkaloids, epipodophyllotoxins, actinomycin D, and Paclitaxel, is to limit their presence inside the cells via the transmembrane protein P-glycoprotein (P-gp), which is encoded by the multidrug resistance (MDR-1) gene (1, 2). P-gp is an ATP-dependent multidrug transporter that is capable of actively pumping a variety of agents out of cells. Injection of unlabeled efflux pump substrates increases retention of radioactivity in the tumor rather than lessen the radioactivity, as seen with receptor-binding radiotracers. Overexpression of P-gp in tumor cells (such as renal carcinoma, hepatoma, pheochromocytoma, and colon carcinoma) leads to resistance to anticancer drugs (3). P-gp is also present in a variety of normal cells, such as intestinal mucosal cells, hepatocytes, renal proximal tubule epithelial cells, and endothelial cells of the blood-brain barrier (BBB) (4). Calcium channel blockers, cyclosporin A, and its non-immunosuppressive analog PSC 833 are MDR modulators, inhibiting transport of P-gp substrates out of the cells (5, 6). Sestamibi (MIBI) is a substrate for P-gp, 99mTc-MIBI has been approved by the U.S. Food and Drug Administration as a myocardial perfusion imaging agent with single-photon emission computed tomography (SPECT) to assess the risk of future cardiac events. It is also used as a tumor-imaging agent in breast, lung, thyroid, and brain cancers. Verapamil, a calcium channel blocker, is also a transport substrate for the P-gp efflux pump (7). [11C]Verapamil is being developed as a positron emission tomography (PET) agent for studying P-gp function non-invasively.

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