Multimodal Imaging of Orthotopic Mouse Model of Endometrial Carcinoma

被引:32
作者
Haldorsen, Ingfrid S. [1 ,2 ]
Popa, Mihaela [3 ]
Fonnes, Tina [4 ]
Brekke, Njal [5 ]
Kopperud, Reidun [4 ]
Visser, Nicole C. [6 ]
Rygh, Cecilie B. [7 ]
Pavlin, Tina [7 ]
Salvesen, Helga B. [4 ,8 ]
McCormack, Emmet [3 ]
Krakstad, Camilla [4 ,8 ]
机构
[1] Haukeland Hosp, Dept Radiol, N-5021 Bergen, Norway
[2] Univ Bergen, Sect Radiol, Dept Clin Med, Bergen, Norway
[3] Univ Bergen, Dept Clin Sci, Bergen, Norway
[4] Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen, Norway
[5] Haukeland Hosp, Dept Radiol, PET Ctr, N-5021 Bergen, Norway
[6] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6525 ED Nijmegen, Netherlands
[7] Univ Bergen, Mol Imaging Ctr, Dept Biomed, Bergen, Norway
[8] Haukeland Hosp, Dept Obstet & Gynaecol, N-5021 Bergen, Norway
关键词
TUMOR XENOGRAFTS; CANCER; THERAPY; GROWTH; MICE;
D O I
10.1371/journal.pone.0135220
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background Orthotopic endometrial cancer models provide a unique tool for studies of tumour growth and metastatic spread. Novel preclinical imaging methods also have the potential to quantify functional tumour characteristics in vivo, with potential relevance for monitoring response to therapy. Methods After orthotopic injection with luc-expressing endometrial cancer cells, eleven mice developed disease detected by weekly bioluminescence imaging (BLI). In parallel the same mice underwent positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) employing F-18-fluorodeoxyglocose (F-18-FDG) or F-18-fluorothymidine (F-18-FLT) and contrast reagent, respectively. The mice were sacrificed when moribund, and post-mortem examination included macroscopic and microscopic examination for validation of growth of primary uterine tumours and metastases. PET-CT was also performed on a patient derived model (PDX) generated from a patient with grade 3 endometrioid endometrial cancer. Results Increased BLI signal during tumour growth was accompanied by increasing metabolic tumour volume (MTV) and increasing MTV x mean standard uptake value of the tumour (SUVmean) in F-18-FDG and F-18-FLT PET-CT, and MRI conspicuously depicted the uterine tumour. At necropsy 82% (9/11) of the mice developed metastases detected by the applied imaging methods. F-18-FDG PET proved to be a good imaging method for detection of patient derived tumour tissue. Conclusions We demonstrate that all imaging modalities enable monitoring of tumour growth and metastatic spread in an orthotopic mouse model of endometrial carcinoma. Both PET tracers, F-18-FDG and F-18-FLT, appear to be equally feasible for detecting tumour development and represent, together with MRI, promising imaging tools for monitoring of patient-derived xenograft (PDX) cancer models.
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页数:17
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