期刊
MOLECULAR IMAGING AND BIOLOGY
卷 19, 期 5, 页码 762-771出版社
SPRINGER
DOI: 10.1007/s11307-017-1051-4
关键词
Positron emission tomography; Magnetic resonance imaging; Contrast enhanced computed tomography; Tumor delineation; Orthotopic mouse model; Colorectal cancer
资金
- University of Antwerp through a Bijzonder Onderzoeksfond [BOF27327]
- iMinds ICON project FIAT
- Innovative Medicines Initiative Joint Undertaking [115151]
- European Union's Seventh Framework Program (FP7)
- EFPIA
Quantification in positron emission tomography (PET) imaging of an orthotopic mouse model of colorectal cancer (CRC) is challenging due to difficult tumor delineation. We aimed to establish a reproducible delineation approach, evaluate its feasibility for reliable PET quantification and compare its added translational value with its subcutaneous counterpart. A subcutaneous Colo205-luc2 tumor fragment harvested from a donor mouse was transplanted onto the caecum of nude mice, with (n = 10) or without (n = 10) the addition of an X-ray detectable thread. Animals underwent 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) PET imaging, complemented with X-ray computed tomography (CT) and magnetic resonance imaging (MRI, 7T). Animals without a thread underwent additional contrast enhanced (Exitron) CT imaging. Tumors were delineated on the MRI, mu PET image or contrast enhanced mu CT images and correlations between in vivo and ex vivo [F-18]FDG tumor uptake as well as between image-derived and caliper-measured tumor volume were evaluated. Finally, cancer hallmarks were assessed immunohistochemically for the characterization of both models. Our results showed the strongest correlation between both in vivo and ex vivo uptake (r = 0.84, p < 0.0001) and image-derived and caliper-measured tumor volume (r = 0.96, p < 0.0001) when the tumor was delineated on the MR image. Orthotopic tumors displayed an abundance of stroma, higher levels of proliferation (p = 0.0007), apoptosis (p = 0.02), and necrosis (p < 0.0001), a higher number of blood vessels (p < 0.0001); yet lower tumor hypoxia (p < 0.0001) as compared with subcutaneous tumors. This orthotopic mouse model proved to be a promising tool for the investigation of CRC through preclinical imaging studies provided the availability of anatomical MR images for accurate tumor delineation. Furthermore, the tumor microenvironment of the orthotopic tumor resembled more that of human CRC, increasing its likelihood to advance translational nuclear imaging studies of CRC.
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