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 [18F]Fluorodeoxyglucose ([18F]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 [18F]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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5512-5522 |
| Number of pages | 11 |
| Journal | Cancer Research |
| Volume | 76 |
| Issue number | 18 |
| DOIs | |
| State | Published - Sep 15 2016 |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Decoding intratumoral heterogeneity of breast cancer by multiparametric in vivo imaging : A translational study. / Schmitz, Jennifer; Schwab, Julian; Schwenck, Johannes; Chen, Qian; Quintanilla-Martinez, Leticia; Hahn, Markus; Wietek, Beate; Schwenzer, Nina; Staebler, Annette; Kohlhofer, Ursula; Aina, Olulanu H.; Hubbard, Neil; Reischl, Gerald; Borowsky, Alexander D; Brucker, Sara; Nikolaou, Konstantin; La Fougère, Christian; Cardiff, Robert; Pichler, Bernd J.; Schmid, Andreas M.
In: Cancer Research, Vol. 76, No. 18, 15.09.2016, p. 5512-5522.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Decoding intratumoral heterogeneity of breast cancer by multiparametric in vivo imaging
T2 - A translational study
AU - Schmitz, Jennifer
AU - Schwab, Julian
AU - Schwenck, Johannes
AU - Chen, Qian
AU - Quintanilla-Martinez, Leticia
AU - Hahn, Markus
AU - Wietek, Beate
AU - Schwenzer, Nina
AU - Staebler, Annette
AU - Kohlhofer, Ursula
AU - Aina, Olulanu H.
AU - Hubbard, Neil
AU - Reischl, Gerald
AU - Borowsky, Alexander D
AU - Brucker, Sara
AU - Nikolaou, Konstantin
AU - La Fougère, Christian
AU - Cardiff, Robert
AU - Pichler, Bernd J.
AU - Schmid, Andreas M.
PY - 2016/9/15
Y1 - 2016/9/15
N2 - 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 [18F]Fluorodeoxyglucose ([18F]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 [18F]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.
AB - 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 [18F]Fluorodeoxyglucose ([18F]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 [18F]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.
UR - http://www.scopus.com/inward/record.url?scp=84988939360&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84988939360&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-15-0642
DO - 10.1158/0008-5472.CAN-15-0642
M3 - Article
C2 - 27466286
AN - SCOPUS:84988939360
VL - 76
SP - 5512
EP - 5522
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 18
ER -