title: Evaluation of treatment response of cilengitide in an experimental model of breast cancer bone metastasis using dynamic PET with 18F-FDG.
abstract: The purpose of this study was the assessment of the feasibility of dynamic positron emission tomography (PET) studies with fluorine-18 fluorodeoxyglucose ((18)F-FDG) to quantify effects of the cyclic Arg-Gly-Asp peptide cilengitide, which targets the ανβ 3 and ανβ 5 integrin receptors in rats with breast cancer bone metastases. Rats were inoculated with MDA-MB-231 breast cancer cells, followed by the development of lytic lesions in the hind leg. Rats with lytic lesions were treated with cilengitide five times weekly on a continuous basis from days 30 to 55 after tumor cell inoculation. Dynamic PET studies with (18)F-FDG were performed in untreated (n=9), controlled (n=4) and treated rats (n=6). The data were assessed using learning-machine two-tissue compartmental analysis. The (18)F-FDG kinetic parameters obtained by two-tissue compartmental model learning-machine showed significant differences when individual parameters were compared between the control group and treated animals. Quantitative assessment of the tracer kinetics and the application of classification analysis to the data provided us with evidence to identify those tumors that demonstrated effect of cilengitide treatment. The transport rate K1 and the phosphorylation rate k3 were significantly different (P=0.033 and 0.038, respectively). Classification analysis based on support vector machines ranking feature elimination of the combination of PET parameters revealed an overall accuracy of 80.0% between treated animals and the control group. We were able to identify 83.3% treated animals compared with the control group based on k2 and VB. In conclusion, the results revealed that cilengitide treatment of experimental breast cancer bone metastases had a significant therapeutic impact on (18)F-FDG kinetics.
authors.affiliation: Clinical Cooperation Unit, Nuclear Medicine, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. c.cheng@dkfz.de
authors.forename: Caixa
authors.initials: C
authors.lastname: Cheng
authors.forename: Dorde
authors.initials: D
authors.lastname: Komljenovic
authors.forename: Leyun
authors.initials: L
authors.lastname: Pan
authors.forename: Antonia
authors.initials: A
authors.lastname: Dimitrakopoulou-Strauss
authors.forename: Ludwig
authors.initials: L
authors.lastname: Strauss
authors.forename: Tobias
authors.initials: T
authors.lastname: Bäuerle
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D005947:Glucose / Q000378:metabolism; D006801:Humans; D049268:Positron-Emission Tomography; D051381:Rats; D012910:Snake Venoms / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D012910:Snake Venoms; D019788:Fluorodeoxyglucose F18; C422910:Cilengitide; D005947:Glucose