title: In vivo monitoring of natural killer cell-dependent clearance of lung metastasis using dynamic positron emission tomography.
abstract: Immunohistological methods indicated a rapid onset of cellular defence shortly after seeding of mammary adenocarcinoma cells into the lungs of F344 rats. The purpose of the present study was to monitor natural killer (NK) cell-mediated effects on tumour cell clearance in vivo, in this model of lung metastasis using dynamic positron-emission tomography (dPET). MADB106 breast cancer cells were labelled with 2'-[(18)F]-2'-deoxy-D-glucose (FDG) then injected intravenously, after the F344 rats had been anaesthetized and placed in a PET scanner. NK cell-depleted and sham-treated control rats were investigated in parallel. The radioactivity per region of interest (ROI) over the lungs peaked at 60 s past injection and was followed by a slow decline over the observation time of 40 min in both groups. Statistical analysis using a linear mixed model revealed that release of radioactivity from tumour cells or tumour cell disintegration was significantly slower in animals after depletion of NK cells compared with controls. There was no significant tumour cell homing in organs other than the lungs. Early kinetics of tumour cells after injection were defined. PET with FDG was shown to be an adequate method to further investigate novel options for using cellular host defence mechanisms in cancer patients.
authors.affiliation: Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany. kruschinski.carsten@mh-hannover.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Kruschinski
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hama
authors.forename: Thomas
authors.initials: T
authors.lastname: Skripuletz
authors.forename: Bernhard
authors.initials: B
authors.lastname: Vaske
authors.forename: Wolfram H
authors.initials: WH
authors.lastname: Knapp
authors.forename: Reinhold E
authors.initials: RE
authors.lastname: Schmidt
authors.forename: Reinhard
authors.initials: R
authors.lastname: Pabst
authors.forename: Stephan
authors.initials: S
authors.lastname: von Hörsten
authors.forename: Michael
authors.initials: M
authors.lastname: Hofmann
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000276:immunology / Q000556:secondary*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D045744:Cell Line, Tumor / Q000637:transplantation; D002465:Cell Movement; D058948:Cell Tracking; D003602:Cytotoxicity, Immunologic; D005240:Feasibility Studies; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000556:secondary*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D013047:Specific Pathogen-Free Organisms; D014018:Tissue Distribution; D014185:Transplantation, Isogeneic
chemical_list: D000911:Antibodies, Monoclonal; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18