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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.  

Author information

Schmitz J1, Schwab J1, Schwenck J2, Chen Q3, Quintanilla-Martinez L4, Hahn M5, Wietek B6, Schwenzer N6, Staebler A4, Kohlhofer U4, Aina OH3, Hubbard NE3, Reischl G1, Borowsky AD3, Brucker S5, Nikolaou K7, la Fougère C8, Cardiff RD3, Pichler BJ9, Schmid AM10.

1Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany.

2Department 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.

3Center for Comparative Medicine, University of California, Davis, California.

4Department of Pathology, Eberhard Karls University Tuebingen, Tuebingen, Germany.

5Department of Women's Health, Eberhard Karls University Tuebingen, Tuebingen, Germany.

6Department of Diagnostic and Interventional Radiology, Eberhard Karls University, Tuebingen, Germany.

7Department of Diagnostic and Interventional Radiology, Eberhard Karls University, Tuebingen, Germany. German Cancer Consortium, German Cancer Research Center, Tuebingen, Germany.

8Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard Karls University Tuebingen, Tuebingen, Germany. German Cancer Consortium, German Cancer Research Center, Tuebingen, Germany.

9Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany. German Cancer Consortium, German Cancer Research Center, Tuebingen, Germany.

10Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany. a.schmid@med.uni-tuebingen.de.