title: Preclinical evaluation of the anti-tumor effects of the natural isoflavone genistein in two xenograft mouse models monitored by [18F]FDG, [18F]FLT, and [64Cu]NODAGA-cetuximab small animal PET.
abstract: The natural phytoestrogen genistein is known as protein kinase inhibitor and tumor suppressor in various types of cancers. We studied its antitumor effect in two different xenograft models using positron emission tomography (PET) in vivo combined with ex vivo histology and nuclear magnetic resonance (NMR) metabolic fingerprinting.
  
  
  METHODS
  A431 and Colo205 tumor-bearing mice were treated with vehicle or genistein (500 mg/kg/d) over a period of 12 days. Imaging was performed with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and 3'-deoxy-3'-[18F]fluorothymidine ([18F] FLT). In a second study A431 tumor-bearing mice were treated with vehicle, genistein (500 mg/kg/d), cetuximab (1 mg/3d) or a combination of the compounds and imaged using [18F]FDG, [18F]FLT and [64Cu]NODAGA-cetuximab. Data were compared to histology and principal components analysis (PCA) of NMR fingerprinting data.
  
  
  RESULTS
  Genistein reduced tumor growth significantly in both xenografts. [18F] FLT uptake was consistent in both models and corresponded to histological findings and also PCA whereas [18F]FDG and [64Cu]NODAGA-cetuximab were not suitable for therapy monitoring.
  
  
  CONCLUSIONS
  As mono-therapy the natural isoflavone genistein has a powerful therapeutic effect in vivo on A431 and Colo205 tumors. [18F]FLT has superior consistency compared to the other tested tracers in therapy monitoring, while the treatment effect could be shown on the molecular level by histology and metabolic fingerprinting.
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University, Tuebingen, Germany.
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Honndorf
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University, Tuebingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiehr
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University, Tuebingen, Germany.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Rolle
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University, Tuebingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Schmitt
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University, Tuebingen, Germany.
authors.forename: Luisa
authors.initials: L
authors.lastname: Kreft
authors.affiliation: Institute of Pathology, University Hospital, Eberhard Karls University, Tuebingen, Germany.
authors.forename: Letitia
authors.initials: L
authors.lastname: Quintanilla-Martinez
authors.affiliation: Institute of Pathology, University Hospital, Eberhard Karls University, Tuebingen, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Kohlhofer
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University, Tuebingen, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Reischl
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University, Tuebingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Maurer
authors.affiliation: Medical Proteome Center, Institute for Ophthalmic Research, Eberhard Karls University, Tuebingen, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Boldt
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Toxicology, Eberhard Karls University, Tuebingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schwarz
authors.affiliation: Department of Radiology, Diagnostic and Interventional Radiology, Eberhard Karls University, Tuebingen, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University, Tuebingen, Germany.
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Pichler
mesh_terms: D000085:Acetates; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000068818:Cetuximab / Q000494:pharmacology; D003301:Copper Radioisotopes; D015224:Dideoxynucleosides; D019788:Fluorodeoxyglucose F18; D019833:Genistein / Q000494:pharmacology*; D006573:Heterocyclic Compounds, 1-Ring; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes; D023041:Xenograft Model Antitumor Assays
chemical_list: C572723:1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane; D000085:Acetates; D016588:Anticarcinogenic Agents; D003301:Copper Radioisotopes; C000615411:Copper-64; D015224:Dideoxynucleosides; D006573:Heterocyclic Compounds, 1-Ring; D011868:Radioisotopes; D019788:Fluorodeoxyglucose F18; D019833:Genistein; C002854:alovudine; D000068818:Cetuximab
keywords: A431 and Colo205 xenografts; PET; genistein and cetuximab; molecular tumor imaging