title: Multimodal In Vivo Imaging of Tumorigenesis and Response to Chemotherapy in a Transgenic Mouse Model of Mammary Cancer.
abstract: Transgenic mice expressing the polyoma middle T oncoprotein (PyMT) in the mammary epithelium were explored by multimodal imaging to monitor longitudinally spontaneous tumor growth and response to chemotherapy.
  
  
  
  Positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT), single photon emission tomography (SPECT) with [(99m)Tc]TcO4 ([(99m)Tc]TEC), X-ray computed tomography, and fluorescent confocal endomicroscopy (FCE) images were acquired during tumor progression in female PyMT mice. Imaging with [(18)F]FDG and [(99m)Tc]TEC was also performed in untreated, doxorubicin-treated, and docetaxel-treated PyMT mice. Total tumor volumes were quantified. Tumors were collected and macroscopic and histological examinations were performed.
  
  
  
  All PyMT mice developed multifocal tumors of the mammary epithelium that became palpable at 8 weeks of age (W8). Computed tomography (CT) detected tumors at W14, while a clear tumoral uptake of [(99m)Tc]TEC and [(18)F]FDG was present as early as W6 and W8, respectively. No contrast between mammary tumors and surrounding tissue was observed at any stage with [(18)F]FLT. FCE detected an angiogenic switch at W10. Lung metastases were not clearly evidenced by imaging. Doxorubicin and docetaxel treatments delayed tumor growth, as shown by [(18)F]FDG and [(99m)Tc]TEC, but tumor growth resumed upon treatment discontinuation. Tumor growth fitted an exponential model with time constant rates of 0.315, 0.145, and 0.212 week(-1) in untreated, doxorubicin, and docetaxel groups, respectively.
  
  
  
  Molecular imaging of mammary tumors in PyMT is precocious, precise, and predictive. [(18)F]FDG-PET and [(99m)Tc]TEC SPECT monitor tumor response to chemotherapy.
authors.affiliation: CEA, DSV, I2BM, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, Orsay, France.|Service de Médecine nucléaire, Institut Curie, Hôpital René Huguenin, Saint-Cloud, France.|Faculté de Médecine, Université Versailles Saint-Quentin, Versailles, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Alberini
authors.affiliation: CEA, DSV, I2BM, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, Orsay, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Boisgard
authors.affiliation: CEA, DSV, I2BM, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, Orsay, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Guillermet
authors.affiliation: CEA, DSV, I2BM, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, Orsay, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Siquier
authors.affiliation: CEA, DSV, I2BM, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, Orsay, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Jego
authors.affiliation: CEA, DSV, I2BM, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, Orsay, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Thézé
authors.affiliation: Service de pharmacologie, Institut Curie, Hôpital René Huguenin, Saint-Cloud, France.
authors.forename: Saik
authors.initials: S
authors.lastname: Urien
authors.affiliation: Service de pharmacologie, Institut Curie, Hôpital René Huguenin, Saint-Cloud, France.
authors.forename: Keyvan
authors.initials: K
authors.lastname: Rezaï
authors.affiliation: Service de pathologie, Institut Curie, Hôpital René Huguenin, Saint-Cloud, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Menet
authors.affiliation: CEA, DSV, I2BM, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, Orsay, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Maroy
authors.affiliation: CEA, DSV, I2BM, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, Orsay, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dollé
authors.affiliation: CEA, DSV, I2BM, Service Hospitalier Frédéric Joliot, Laboratoire d'Imagerie Moléculaire Expérimentale, Orsay, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Kühnast
authors.affiliation: Université Paris Descartes Sorbonne Paris Cité, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Radiology Department, Paris, France. bertrand.tavitian@inserm.fr.|Université Paris Descartes Sorbonne Paris Cité, INSERM UMR 970, Cardiovascular Research Center - PARCC, 56 rue Leblanc, 75015, Paris, France. bertrand.tavitian@inserm.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tavitian
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D063646:Carcinogenesis / Q000473:pathology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005453:Fluorescence; D019788:Fluorodeoxyglucose F18; D019394:Ki-67 Antigen / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D064847:Multimodal Imaging / Q000379:methods*; D013667:Technetium / Q000737:chemistry; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D019788:Fluorodeoxyglucose F18; D013667:Technetium
keywords: Biomarker; Breast cancer; Molecular imaging; Response to treatment; Sodium-iodide symporter; Transgenic model