Use of in vivo bioluminescence imaging to predict hepatic tumor burden in mice.
BACKGROUND
We used bioluminescence imaging (BLI) to validate serial assessment of neoplastic growth within the murine liver. We hypothesized that, in mice bearing luciferase-expressing liver metastases, bioluminescence would reflect neoplastic burden estimated by liver weight.


METHODS
Murine colon carcinoma cells were infected with a retroviral vector encoding luciferase. Bioluminescence was measured in vitro, and in vivo following intrasplenic tumor cell inoculation into Balb/C mice. At varying time intervals, mice were imaged and immediately killed to determine correlation of in vivo and ex vivo BL with liver weight. To examine sensitivity in vivo, we performed direct intrahepatic inoculation.


RESULTS
In vitro, photon emission correlated with increasing cell numbers. In the metastatic model, a statistically significant increase was depicted in both liver weight and bioluminescence 20 days after tumor inoculation compared with earlier time points (P < 0.0001). With progressively increasing tumor burden, however, a poor correlation between in vivo BL and liver weight was observed. When livers with very large tumors were excluded, R(2) = 0.90. In contrast, correlation between ex vivo BL and liver weight remained high throughout the study period (R(2) = 0.94).


CONCLUSIONS
When imaging tumors at end-stages of disease, in vivo BL underestimates actual tumor burden. If context-specific limitations are recognized, however, BLI is a sensitive approach to temporal monitoring of tumor progression in preclinical models.
Sarraf-Yazdi
Shiva
S
Department of Surgery, Duke University Medical Center, Box 31066 DUMC, Durham, NC 27710, USA. sarra002@mc.duke.edu
Mi
Jing
J
Dewhirst
Mark W
MW
Clary
Bryan M
BM
D000818:Animals; D002277:Carcinoma / Q000473:pathology* / Q000556:secondary*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D003952:Diagnostic Imaging; D005260:Female; D018014:Gene Transfer Techniques; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology* / Q000556:secondary*; D008156:Luciferases / Q000235:genetics; D008163:Luminescent Measurements; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009929:Organ Size; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
D008156:Luciferases