Probing Multidrug Resistance P-glycoprotein Transporter Activity with SPECT Radiopharmaceuticals
Authors: Piwnica-Worms, David; Sharma, Vijay
Source: Current Topics in Medicinal Chemistry, Volume 10, Number 17, December 2010 , pp. 1834-1845(12)
Publisher: Bentham Science Publishers
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: Multidrug resistance; ABC transporters; P-glycoprotein; SPECT; PET; metal complexes; radiopharmaceuticals; technetium-99m; blood-brain barrier; cancer; gene therapy; Multidrug Resistance; P-glycoprotein; ABC transporters; 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; Pgp expression; 99mTc-Sestamibi; Multiple myeloma (MM); valspodar; Tariquidar; Parkinsonian syndrome; 11C-verapamil; Alzheimer's Disease (AD); Creutzfeldt-Jakob disease
Document Type: Research article
Publication date: 2010-12-01