Quantitative Detection of Orthotopic Liver Cancer in Mice Using Indocyanine Green and Dynamic Diffuse Fluorescence Tomography Imaging.

Abstract

Orthotopic tumor model has become an essential tool for studying drug biodistribution and tumor progression over time owing to the rapid development of in vivo imaging and immunological science. Dynamic diffuse fluorescence tomography (DFT) is a promising imaging modality that can map the three-dimensional distribution of a fluorophore within the object and capture the metabolic parameters of fluorophores in vivo. It has been widely applied in tumor detection, drug development, and efficacy evaluation. To detect orthotopic liver tumors, we combined indocyanine green (ICG) and a DFT system to perform fluorescence imaging and quantitative analysis for orthotopic liver tumors in mice. The orthotopic liver models were first established, and the liver fluorescence yields were detected in pre- and post-cancerous liver using the DFT system. The results showed that there was higher liver uptake and prolonged retention in orthotopic tumor liver compared to normal liver. Furthermore, the pharmacokinetic parameters suggested the uptake coefficient of tumor liver was above twice that of normal liver, while the excretion rates were similar. Additionally, to intuitively assess tumor occurrence, we propose using normalized fluorescence ratios of 5 and maximum fluorescence values of 0.01 mm^-1 as evaluation criteria. The study demonstrates DFT imaging is a promising tool in orthotopic tumor model detection and drug or agent metabolic evaluation.