Non-invasive imaging of implanted peritoneal carcinomatosis in mice using PET and bioluminescence imaging

Abstract

Background: Non-invasive imaging of peritoneal carcinomatosis remains challenging. The aim of this study was to compare positron emission tomography (PET) and bioluminescence imaging (BLI) for the early detection of peritoneal carcinomatosis in a mouse model.

Methods: Female nude mice were inoculated intraperitoneally with 1×10(7) HSC45-M2-luc gastric cancer cells. The cells were stably transfected with the gene coding for firefly luciferase. Tumour development was monitored using PET and BLI and in two subgroups, on days 3 and 4 or on days 6 and 7 after tumour cell inoculation. Tumour nodules found on post mortem examination served as the reference standard for evaluating the images.

Results: PET detected 58/82 lesions (sensitivity 71 %). This method detected all (100 %) nodules larger than 6 mm, 88 % of nodules in the range of >2-4 mm, and even 58 % of small nodules measuring only 1-2 mm. BLI identified a total of 40/82 lesions (sensitivity 49 %). The difference between PET and BLI was statistically significant at p < 0.05 (PET/BLI chi-square 8.2).

Conclusions: PET was more sensitive than BLI for the detection of early peritoneal carcinomatosis in our mouse model. The sensitivity of BLI largely depended on the site of the lesions in relation to the imaging device.

Fig. 1

Small peritoneal lesion in the small bowel mesentery (white arrow) (a). The tumour measured 1.5 mm in diameter and was detected only with PET (b). The lesion was probably too deep in the abdominal cavity to be detected with BLI (c)

Fig. 2

A 2.5 mm nodule in the para-pancreatic region found at post mortem (white arrow) (a). The lesion was detected easily with PET (b) and BLI (c) (white arrows). There were two false-positive sites on PET that could not be documented at post mortem (small white arrows) (b)

Fig. 3

Post mortem finding of a 5.5-mm para-pancreatic lesion and a 4-mm lesion in small bowel mesentery (white arrows) (a). Both nodules were detected with PET (b). The lesion in small bowel mesentery remained undetected with BLI, most likely due to the site being covered by other bowel structures (c)

Fig. 4

Correlation of BLI light signal (mean grey level intensity) and tumour volume in the para-pancreatic area determined post mortem. No significant correlation could be noted (Spearman rank correlation coefficient r = 0.2978, n.s.). A mild correlation is suggested by visual interpretation of the trend line. One larger lesion (16 mm³) remained undetected because it was covered by the left liver lobe