Multimodal In Vivo Imaging of Tumorigenesis and Response to Chemotherapy in a Transgenic Mouse Model of Mammary Cancer

Jean-Louis Alberini (1, 2, 3) , Raphael Boisgard (1) , Stéphanie Guillermet (1) , Karine Siquier (1) , Benoît Jego (1) , Benoît Thézé (4, 1) , Saik Urien (2) , Keyvan Rezaï (2) , Emmanuelle Menet (2) , Renaud Maroy (5, 1) , Frédéric Dollé (1) , Bertrand Kühnast (1) , Bertrand Tavitian (6, 7)

1 LIME - Laboratoire d'Imagerie Moléculaire Expérimentale
2 CRLCC René Huguenin - CRLCC René Huguenin
3 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines
4 IMIV - U1023 - ERL9218 - Imagerie Moléculaire in Vivo
5 SHFJ - Service Hospitalier Frédéric Joliot
6 PARCC - UMR-S U970 - Paris-Centre de Recherche Cardiovasculaire
7 HEGP - Hôpital Européen Georges Pompidou [APHP]

Purpose: 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. Procedures: 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]TcO 4 ([ 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. Results: 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. Conclusions: Molecular imaging of mammary tumors in PyMT is precocious, precise, and predictive. [18F]FDG-PET and [99mTc]TEC SPECT monitor tumor response to chemotherapy.

Mots clés: Response to treatment; Breast cancer; Biomarker; Molecular imaging; Transgenic model; Sodium-iodide symporter

Domaines: Cancer; Imagerie; Pharmacologie

Jean-Louis Alberini, Raphael Boisgard, Stéphanie Guillermet, Karine Siquier, Benoît Jego, et al.. Multimodal In Vivo Imaging of Tumorigenesis and Response to Chemotherapy in a Transgenic Mouse Model of Mammary Cancer. Molecular Imaging and Biology, 2016, 18 (4), pp.617-626. ⟨10.1007/s11307-015-0916-7⟩. ⟨hal-01874014⟩