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Probing Multidrug Resistance P-glycoprotein Transporter Activity with SPECT Radiopharmaceuticals

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Abstract:

Multidrug resistance (MDR) mediated by overexpression of MDR1 (ABCB1) P-glycoprotein (Pgp) is one of the best characterized transporter-mediated barriers to successful chemotherapy in cancer patients and is also a rapidly emerging target in the progression of neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. Therefore, molecular imaging probes capable of imaging noninvasively Pgp and closely related transporter activities in tissues as well as tumors would be expected to contribute to personalized medicine. Interrogation of Pgp-mediated transport activity in vivo via noninvasive SPECT imaging could be beneficial for stratification of patient populations likely to benefit from a given therapeutic treatment, assist in the management of chemotherapy and aid the study of neurodegenerative diseases.

Keywords: 11C-verapamil; 99mTc-Furifosmin; 99mTc-Sestamibi; ABC transporters; ATP-binding cassette (ABC); Alzheimer's Disease (AD); Blood-brain barrier; Cancer; Creutzfeldt-Jakob disease; Cyclosporin; Gene therapy; LY335979; Metal complexes; Multidrug Resistance; Multidrug resistance; Multiple myeloma (MM); Nucleotide-binding domains (NBDs); P-glycoprotein; PET; PSC 833; Parkinsonian syndrome; Pgp activity; Pgp expression; Pgp inhibitors; Pgp substrate; Q-complexes; Quinidine; Radiopharmaceuticals; SPECT; Schiff-base Ga(III) complexes; Tariquidar; Technetium-99m; Transmembrane domains; Verapamil; blood-brain barrier; cancer; gene therapy; metal complexes; radiopharmaceuticals; technetium-99m; valspodar

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/156802610792928086

Affiliations: Mallinckrodt Institute of Radiology, Washington University Medical School, Box 8225, 510 S.Kingshighway Blvd. St. Louis, MO 63110.

Publication date: December 1, 2010

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