title: Imaging multidrug resistance with 4-[18F]fluoropaclitaxel.
abstract: Multidrug resistance (MDR) is a cause of treatment failure in many cancer patients. MDR refers to a phenotype whereby a tumor is resistant to a large number of natural chemotherapeutic drugs. Having prior knowledge of the presence of such resistance would decrease morbidity from unsuccessful therapy and allow for the selection of individuals who may benefit from the coadministration of MDR-inhibiting drugs. The Tc-99m-labeled single-photon-emitting radiotracers sestamibi and tetrofosmin have shown some predictive value. However, positron-emitting radiotracers, which allow for dynamic quantitative imaging, hold promise for a more accurate and specific identification of MDRtumors.MDR-expressing tumors are resistant to paclitaxel, which is commonly used as a chemotherapeutic agent. 4-[18F]Fluoropaclitaxel (FPAC) is a PET-radiolabeled analogue of paclitaxel. Preclinical studies have shown the uptake of FPAC to be inversely proportional to tumor MDR expression. FPAC PET imaging in normal volunteers shows biodistribution to be similar to that in nonhuman primates. Imaging in a breast cancer patient showed FPAC localization in a primary tumor that responded to chemotherapy, while failure to localize in mediastinal disease corresponded with only partial response.FPAC PET imaging shows promise for the noninvasive pretreatment identification of MDR-expressing tumors. While much additional work is needed, this work represents a step toward image-guided personalized medicine.
authors.affiliation: Department of Radiology, Virginia Commonwealth University, Richmond, VA, USA. kurdziel@vcu.edu
authors.forename: Karen A
authors.initials: KA
authors.lastname: Kurdziel
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Kalen
authors.forename: Jerry I
authors.initials: JI
authors.lastname: Hirsch
authors.forename: John D
authors.initials: JD
authors.lastname: Wilson
authors.forename: Rakesh
authors.initials: R
authors.lastname: Agarwal
authors.forename: Daniel
authors.initials: D
authors.lastname: Barrett
authors.forename: Harry D
authors.initials: HD
authors.lastname: Bear
authors.forename: James F
authors.initials: JF
authors.lastname: McCumiskey
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D017239:Paclitaxel / Q000031:analogs & derivatives*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals
chemical_list: D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; C526531:4-fluoropaclitaxel; D017239:Paclitaxel