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Probing Multidrug Resistance P-glycoprotein Transporter Activity with SPECT Radiopharmaceuticals

[ Vol. 10 , Issue. 17 ]

Author(s):

David Piwnica-Worms and Vijay Sharma   Pages 1834 - 1845 ( 12 )

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 Alzheimers and Parkinsons 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:

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

Affiliation:

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



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