Longitudinal in vivo susceptibility contrast MRI measurements of LS174T colorectal liver metastasis in nude mice.
OBJECTIVE
To characterize longitudinal tumor progression in a murine orthotopic model of liver metastasis using susceptibility contrast magnetic resonance imaging (MRI).


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.


CONCLUSIONS
Susceptibility-contrast MRI using a single dose of feruglose can be used to easily detect and longitudinally monitor orthotopically propagated liver metastases in vivo.
Kalber
Tammy L
TL
Cancer Research UK Biomedical Magnetic Resonance Research Group, Division of Basic Medical Sciences, St. George's, University of London, London, UK.
Waterton
John C
JC
Griffiths
John R
JR
Ryan
Anderson J
AJ
Robinson
Simon P
SP
D000818:Animals; D001562:Benzimidazoles; D015179:Colorectal Neoplasms / Q000473:pathology*; D003911:Dextrans; D018450:Disease Progression; D052203:Ferrosoferric Oxide; D000860:Hypoxia; D007089:Image Enhancement / Q000379:methods; D007091:Image Processing, Computer-Assisted; D007501:Iron; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000556:secondary*; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D009368:Neoplasm Transplantation; D010087:Oxides
D001562:Benzimidazoles; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D007501:Iron; C065507:ferumoxides; C017807:bisbenzimide ethoxide trihydrochloride; D052203:Ferrosoferric Oxide