Multimodal imaging of the same mouse by MRI, ¹⁸F-FDG PET, ¹⁸F-FLT PET and BLI.

<p>MRI three weeks presacrificed (A) depicting large uterine tumour tissue in the left uterine horn (thin arrows) with intrauterine fluid cranial of the tumour (filled large arrow) and small amounts of free intraperitoneal fluid cranial to the right kidney (K) (small arrows). The tumour tissue is moderately enhancing on T1-weighted series after contrast and the tumour exhibits restricted diffusion with hyperintensity on high b-value DWI with corresponding low apparent diffusion coefficient (ADC) value (1.11 x 10⁻³ mm²/s) on the ADC map (A). BLI 4 to 1 weeks presacrificed (B) shows increasing BLI signal corresponding to the tumour of the left uterine horn; the corresponding tumour tissue was evident macroscopically and confirmed microscopically at necropsy (B). ¹⁸F-FDG PET-CT two weeks presacrificed (C) depicts a large ¹⁸F-FDG-avid tumour in the left uterine horn (arrows) with estimated metabolic tumour volume of 33 ml. ¹⁸F-FLT PET-CT one week presacrificed (D) depicts large ¹⁸F-FLT-avid tumour in the left uterine horn (arrows) with estimated metabolic tumour volume of 44 ml. ¹⁸F-FDG/¹⁸F-FLT-avidity in a VOI in the nuchal muscular tissue (C and D; small arrows) was used as reference tissue to define a threshold for likely tumour tissue (activity of x2 and of x6 for ¹⁸F-FLT and ¹⁸F-FDG, respectively) to be included in the estimated metabolic tumour volume. B: bladder; H: heart.</p

Histological evaluations of tumour characteristics and spread of disease.

<p>Organs were fixed in formaldehyde, sectioned and stained with HE to confirm presence of tumour tissue and for histological characterization of tumour. Sections from a representative mouse depict a large tumour mass in the left uterine horn (A) with necrotic tissue in the centre. Normal uterine morphology is seen in the right uterine horn with endometrial glands and normal stroma and myometrium. Detail of tumour in the left uterine horn (B) reveals solid growing tumour, resembling a grade 3 endometrioid endometrial cancer. Solid tumour masses were also detected in ovaries (C). Inguinal lymph node, macroscopically suspected to be metastatic, was confirmed to represent a metastasis (D), however, without visible surrounding lymphoid tissue. Solid tumour components are depicted in the pancreas (E) with tumour tissue infiltrating surrounding fat tissue. Metastasis is observed on the outer surface of the liver (F), and tumour tissue is also detected in blood vessels of the lung (G), the latter indicating hematogenous spread.</p

Orthotopic injection of Ishikawa^Luc cells results in weight loss and reduced survival.

<p>Mice injected with Ishikawa^Luc cells were monitored weekly for signs of disease development. Weight loss (A) was detected as an early sign of disease. Mice developing symptoms of severe disease were sacrificed and the overall survival is visualized in a Kaplan-Meier survival plot (B).</p

Tumour growth monitored by Bioluminescence Imaging (BLI).

<p>Tumour growth was monitored weekly by <i>in vivo</i> BLI and an increase in the net bioluminescence versus time was observed (A, B). Organs were also examined by BLI post-mortem to visualize metastatic spread (C). Strong BLI signals were detected at site of injection (left uterine horn; luh), right ovary (o), connective tissue surrounding the uterine horn (ct), pancreas (p) and metastatic node (mn). Spot signals were detected in the liver (l), spleen (s), kidneys (k), heart (h) and lung (lu). No signal was detected in adrenal gland (a).</p

Tumour growth monitored by PET-CT.

<p>Tumour growth in the left uterine horn (A) and growth of abdominal metastasis (B) measured by ¹⁸F-FLT PET-CT at 5, 6 and 7 weeks after inoculation of cells; and by ¹⁸F-FDG PET-CT 8 weeks after inoculation (A and B) in the same mouse. Estimated metabolic tumour volume increased from 5 to 7 weeks after inoculation based on ¹⁸F-FLT PET-CT but was stable or slightly decreased from 7 to 8 weeks after inoculation based on ¹⁸F-FLT PET-CT (week 7) and ¹⁸F-FDG PET-CT (week 8) (C/D, G/H). The estimated ¹⁸F-FLT-SUV_mean x MTV steadily increased from 5 to 7 weeks after inoculation in both the primary tumour (E) and in the metastasis (I). Panel F and J show Total Lesion Glycolysis (¹⁸F-FDG-SUV_mean x MTV) for primary tumor and metastasis, respectively. Histologic examination of the uterus (K) and the pancreas (L) validated presence of malignant tissue (asterisks) as detected with PET-CT.</p

Tumour development and metastasis dissemination in Ishikawa^Luc model.

<p><i>NA</i>: <i>Not applicable</i>.</p><p><i>Total number of mice with organs affected by disease</i>, <i>defined by positive BLI signal and presence of cancer cells in histologic sections</i>.</p