TY - JOUR
T1 - Intratumoral in vivo staging of breast cancer by multi-tracer PET and advanced analysis
AU - Griessinger, Jennifer
AU - Schwab, Julian
AU - Chen, Qian
AU - Kühn, Anna
AU - Cotton, Jonathan
AU - Bowden, Gregory
AU - Preibsch, Heike
AU - Reischl, Gerald
AU - Quintanilla-Martinez, Leticia
AU - Mori, Hidetoshi
AU - Dang, An Nguyen
AU - Kohlhofer, Ursula
AU - Aina, Olulanu H.
AU - Borowsky, Alexander D.
AU - Pichler, Bernd J.
AU - Cardiff, Robert D.
AU - Schmid, Andreas M.
N1 - Funding Information:
We would like to thank Maren Harant, Ramona Stumm, Funda Cay, Natalie Mucha, Daniel Bukala, Neil Hubbard, and Sandro Aidone for their excellent technical assistance. Further, parts of this work were included in the doctoral thesis of Jennifer Griessinger, nee Schmitz. Parts of this work were funded by fortüne grant 2223-0-0, the Swiss Werner Siemens Foundation, the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC 2180—390900677 and Institutional Strategy of the University of Tübingen (Deutsche Forschungsgemeinschaft, ZUK 63).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - The staging and local management of breast cancer involves the evaluation of the extent and completeness of excision of both the invasive carcinoma component and also the intraductal component or ductal carcinoma in situ. When both invasive ductal carcinoma and coincident ductal carcinoma in situ are present, assessment of the extent and localization of both components is required for optimal therapeutic planning. We have used a mouse model of breast cancer to evaluate the feasibility of applying molecular imaging to assess the local status of cancers in vivo. Multi-tracer positron emission tomography (PET) and magnetic resonance imaging (MRI) characterize the transition from premalignancy to invasive carcinoma. PET tracers for glucose consumption, membrane synthesis, and neoangiogenesis in combination with a Gaussian mixture model-based analysis reveal image-derived thresholds to separate the different stages within the whole-lesion. Autoradiography, histology, and quantitative image analysis of immunohistochemistry further corroborate our in vivo findings. Finally, clinical data further support our conclusions and demonstrate translational potential. In summary, this preclinical model provides a platform for characterizing multistep tumor progression and provides proof of concept that supports the utilization of advanced protocols for PET/MRI in clinical breast cancer imaging.
AB - The staging and local management of breast cancer involves the evaluation of the extent and completeness of excision of both the invasive carcinoma component and also the intraductal component or ductal carcinoma in situ. When both invasive ductal carcinoma and coincident ductal carcinoma in situ are present, assessment of the extent and localization of both components is required for optimal therapeutic planning. We have used a mouse model of breast cancer to evaluate the feasibility of applying molecular imaging to assess the local status of cancers in vivo. Multi-tracer positron emission tomography (PET) and magnetic resonance imaging (MRI) characterize the transition from premalignancy to invasive carcinoma. PET tracers for glucose consumption, membrane synthesis, and neoangiogenesis in combination with a Gaussian mixture model-based analysis reveal image-derived thresholds to separate the different stages within the whole-lesion. Autoradiography, histology, and quantitative image analysis of immunohistochemistry further corroborate our in vivo findings. Finally, clinical data further support our conclusions and demonstrate translational potential. In summary, this preclinical model provides a platform for characterizing multistep tumor progression and provides proof of concept that supports the utilization of advanced protocols for PET/MRI in clinical breast cancer imaging.
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U2 - 10.1038/s41523-022-00398-x
DO - 10.1038/s41523-022-00398-x
M3 - Article
AN - SCOPUS:85127115196
VL - 8
JO - npj Breast Cancer
JF - npj Breast Cancer
SN - 2374-4677
IS - 1
M1 - 41
ER -