title: Decoding Intratumoral Heterogeneity of Breast Cancer by Multiparametric In Vivo Imaging: A Translational Study.
abstract: Differential diagnosis and therapy of heterogeneous breast tumors poses a major clinical challenge. To address the need for a comprehensive, noninvasive strategy to define the molecular and functional profiles of tumors in vivo, we investigated a novel combination of metabolic PET and diffusion-weighted (DW)-MRI in the polyoma virus middle T antigen transgenic mouse model of breast cancer. The implementation of a voxelwise analysis for the clustering of intra- and intertumoral heterogeneity in this model resulted in a multiparametric profile based on [(18)F]Fluorodeoxyglucose ([(18)F]FDG)-PET and DW-MRI, which identified three distinct tumor phenotypes in vivo, including solid acinar, and solid nodular malignancies as well as cystic hyperplasia. To evaluate the feasibility of this approach for clinical use, we examined estrogen receptor-positive and progesterone receptor-positive breast tumors from five patient cases using DW-MRI and [(18)F]FDG-PET in a simultaneous PET/MRI system. The postsurgical in vivo PET/MRI data were correlated to whole-slide histology using the latter traditional diagnostic standard to define phenotype. By this approach, we showed how molecular, structural (microscopic, anatomic), and functional information could be simultaneously obtained noninvasively to identify precancerous and malignant subtypes within heterogeneous tumors. Combined with an automatized analysis, our results suggest that multiparametric molecular and functional imaging may be capable of providing comprehensive tumor profiling for noninvasive cancer diagnostics. Cancer Res; 76(18); 5512-22. ©2016 AACR.
authors.affiliation: Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schmitz
authors.affiliation: Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Schwab
authors.affiliation: Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany. Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schwenck
authors.affiliation: Center for Comparative Medicine, University of California, Davis, California.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pathology, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martinez
authors.affiliation: Department of Women's Health, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Hahn
authors.affiliation: Department of Diagnostic and Interventional Radiology, Eberhard Karls University, Tuebingen, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Wietek
authors.affiliation: Department of Diagnostic and Interventional Radiology, Eberhard Karls University, Tuebingen, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Schwenzer
authors.affiliation: Department of Pathology, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Staebler
authors.affiliation: Department of Pathology, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Kohlhofer
authors.affiliation: Center for Comparative Medicine, University of California, Davis, California.
authors.forename: Olulanu H
authors.initials: OH
authors.lastname: Aina
authors.affiliation: Center for Comparative Medicine, University of California, Davis, California.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Hubbard
authors.affiliation: Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Reischl
authors.affiliation: Center for Comparative Medicine, University of California, Davis, California.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Borowsky
authors.affiliation: Department of Women's Health, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Brucker
authors.affiliation: Department of Diagnostic and Interventional Radiology, Eberhard Karls University, Tuebingen, Germany. German Cancer Consortium, German Cancer Research Center, Tuebingen, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Nikolaou
authors.affiliation: Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard Karls University Tuebingen, Tuebingen, Germany. German Cancer Consortium, German Cancer Research Center, Tuebingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: la Fougère
authors.affiliation: Center for Comparative Medicine, University of California, Davis, California.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Cardiff
authors.affiliation: Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany. German Cancer Consortium, German Cancer Research Center, Tuebingen, Germany.
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Pichler
authors.affiliation: Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany. a.schmid@med.uni-tuebingen.de.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Schmid
mesh_terms: D000368:Aged; D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18