PET Imaging of Multidrug Resistance in Tumors Using 18F-Fluoropaclitaxel
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: 18F-Fluoropaclitaxel; ABC (ATP Binding Cassette); Cytochrome p450; Docetaxel; Drug development; F-18 fluoropaclitaxel; Human breast tumor cell line; MCF tumors; MDR modulator; MIRDOSE; Molecular Imaging; Multidrug Resistance; Multidrug resistance; P-glycoprotein; PET; PET Imaging; Paclitaxel; Pgp; Pgp expression; Pgp inhibitor; Pgp modulation; Phenylisoserine moiety; Standardized uptake value; Taxus baccata; Taxus brevifolia; Tumor cells; XR9576; [18F]FPAC DMSO; [99mTc] sestamibi; [99mTc] tetrofosmin; b-tubulin; chemotherapeutic agent; microPET; tariquidar
Document Type: Research Article
Affiliations: Molecular Imaging Program (MIP)/CCR, National Cancer Institute, 10/B3B403, 10 Center Drive MSC 1180, Bethesda, MD 20892.
Publication date: December 1, 2010