TL Kalber, JC Waterton, JR Griffiths, AJ Ryan, SP Robinson
J Magn Reson Imaging
PURPOSE: To characterize longitudinal tumor progression in a murine orthotopic model of liver metastasis using susceptibility contrast magnetic resonance imaging (MRI). MATERIALS AND METHODS: Nude mice were inoculated intrasplenically with LS174T colorectal carcinoma cells 24 hours postadministration of 2.5 mgFe/kg of the ultrasmall superparamagnetic iron oxide particle preparation feruglose. Contiguous T(2) and T(2)-weighted multislice MR images were acquired 10, 15, 20, 25, 30, and 35 days postinoculation to longitudinally evaluate metastatic progression. Functional tumor vasculature and hypoxia were histologically evaluated at the final timepoint using Hoechst 33342 uptake, pimonidazole and hematoxylin and eosin staining. A parallel cohort of subcutaneous tumors was included for comparison. RESULTS: All intrasplenically inoculated mice developed liver metastases, evident in both T(2)- and T(2)-weighted images as high-signal deposits, compared to feruglose-nulled normal liver. Small lesions were detected as early as day 10 and all mice exhibited progressing lesions over 35 days. Liver metastases took longer to establish, but exhibited a similar volume doubling time to the subcutaneously propagated tumors of approximately 2-3 days. Different functional tumor vascular architectures between the two growth sites were apparent. CONCLUSION: Susceptibility-contrast MRI using a single dose of feruglose can be used to easily detect and longitudinally monitor orthotopically propagated liver metastases in vivo.