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PET Imaging of Multidrug Resistance in Tumors Using 18F-Fluoropaclitaxel

[ Vol. 10 , Issue. 17 ]

Author(s):

Karen A. Kurdziel and Dale O. Kiesewetter   Pages 1792 - 1798 ( 7 )

Abstract:


The failure of solid tumors to respond to chemotherapy is a complicated and clinically frustrating issue. The ability to predict which tumors will respond to treatment could reduce the human and monetary costs of cancer therapy by allowing pro-active selection of a chemotherapeutic to which the tumor does not express resistance. PET/CT imaging with a radiolabeled form of paclitaxel, F-18 fluoropaclitaxel (FPAC), may be able to predict the uptake of paclitaxel in solid tumors, and as a substrate of P-glycoprotein, it may also predict which tumors exhibit multidrug resistance (MDR), a phenotype in which tumors fail to respond to a wide variety of chemically unrelated chemotherapeutic agents. This article reviews the synthetic, preclinical and early human data obtained during the development phase of this promising new radiopharmaceutical.

Keywords:

Drug development, Molecular Imaging, F-18 fluoropaclitaxel, Multidrug resistance, Paclitaxel, PET, Pgp, PET Imaging, 18F-Fluoropaclitaxel, P-glycoprotein, Tumor cells, chemotherapeutic agent, ABC (ATP Binding Cassette), Pgp expression, Cytochrome p450, Taxus brevifolia, Taxus baccata, Docetaxel, b-tubulin, Phenylisoserine moiety, [99mTc] sestamibi, [99mTc] tetrofosmin, tariquidar, XR9576, microPET, Pgp inhibitor, [18F]FPAC DMSO, Human breast tumor cell line, Standardized uptake value, MCF tumors, MIRDOSE, MDR modulator, Pgp modulation

Affiliation:

Molecular Imaging Program (MIP)/CCR, National Cancer Institute, 10/B3B403, 10 Center Drive MSC 1180, Bethesda, MD 20892.



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