title: Positherapy: targeted nuclear therapy of breast cancer with 18F-2-deoxy-2-fluoro-D-glucose.
abstract: Breast cancer remains a major cause of cancer death in women in the United States. Novel therapies are needed for patients when standard treatments are ineffective. We have recently shown on a cellular level the therapeutic potential of positrons in malignancy. Here, we report for the first time positron therapy with (18)F-2-deoxy-2-fluoro-D-glucose ((18)F-FDG) in a breast cancer animal model to affect tumor growth rate and survival (positherapy). We used xenografted mammary tumors in nude mice using Notch mammary cancer cells which also express ras oncogene. Notch xenografted tumors actively took up (18)F-FDG with a tumor to normal tissue ratio of 3.24. Tumor-bearing mice were treated with 2.5 mCi (18)F-FDG, which is equivalent to the physiological human maximum tolerated dose. Positherapy resulted in both significant prolongation of survival and decrease in tumor growth rate in comparison with nontreated controls. Immunoblot of Notch tumors showed the presence of glucose transporters (GLUT) 1, 4, and 8. Substantial differences between GLUT1, GLUT4, and GLUT8 were observed in their distribution within the tumor mass. Whereas GLUT4 and GLUT8 were distributed relatively homogeneously throughout the tumor, GLUT1 was confined to necrotic areas. Immunofluorescence double labeling was used to determine cellular localization of GLUTs. GLUT1 was expressed mostly at the cell membrane. GLUT4 and GLUT8 were mostly localized to cytoplasmic compartments with some GLUT4 expressed at or near the cell membrane in close proximity to GLUT1. Thus, GLUT1 was likely responsible for the (18)F-FDG uptake by tumor cells with some possible contribution from GLUT4. These results are important for the development of positherapy with (18)F-FDG for refractory metastatic breast and other cancers.
authors.affiliation: Department of Nuclear Medicine, Albert Einstein College of Medicine, 1695A Eastchester Road, Bronx, NY 10461, USA.
authors.forename: Renee M
authors.initials: RM
authors.lastname: Moadel
authors.forename: Richard H
authors.initials: RH
authors.lastname: Weldon
authors.forename: Ellen B
authors.initials: EB
authors.lastname: Katz
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.forename: Joseph
authors.initials: J
authors.lastname: Mani
authors.forename: Mark
authors.initials: M
authors.lastname: Stahl
authors.forename: M Donald
authors.initials: MD
authors.lastname: Blaufox
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: Charron
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Dadachova
mesh_terms: D000818:Animals; D005260:Female; D005455:Fluorescent Antibody Technique; D019788:Fluorodeoxyglucose F18 / Q000627:therapeutic use*; D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D015151:Immunoblotting; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy*; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis; D009124:Muscle Proteins / Q000096:biosynthesis; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000627:therapeutic use*
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D019275:Radiopharmaceuticals; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; C498628:Slc2a8 protein, mouse; D019788:Fluorodeoxyglucose F18