To evaluate hepatobiliary-specific
contrast agent (CA)
mangafodipir trisodium (
Mn-DPDP)-enhanced magnetic resonance imaging (MRI) for predicting the therapeutic efficacy of the vascular disrupting agent
combretastatin A4 phosphate (CA4P) in rats with primary and secondary liver
tumors, 36 primary
hepatocellular carcinomas (HCCs) were raised by
diethylnitrosamine gavage in 16 male rats, in 6 of which one
rhabdomyosarcomas (R1) was intrahepatically implanted as secondary liver
tumors. On a 3.0T MR scanner with a wrist coil,
tumors were monitored weekly by T2-/T1-weighted images (T2WI/T1WI) and characterized by
Mn-DPDP-enhanced MRI. CA4P-induced intratumoral
necrosis was depicted by nonspecific
gadoterate meglumine (
Gd-DOTA)-enhanced MRI before and 12 h after
therapy. Changes of
tumor-to-liver contrast (ΔT/L) on
Mn-DPDP-enhanced images were analyzed. In vivo MRI findings were verified by postmortem microangiography and histopathology. Rat models of primary HCCs in a full spectrum of differentiation and secondary R1 liver
tumors were successfully generated.
Mn-DPDP-enhanced ΔT/L was negatively correlated with HCC differentiation grade (P < 0.01).
After treatment with CA4P, more extensive tumoral
necrosis was found in highly differentiated HCCs than that in moderately and poorly differentiated ones (P < 0.01); nearly complete
necrosis was induced in secondary liver
tumors.
Mn-DPDP-enhanced MRI may help in imaging diagnosis of primary and secondary liver
malignancies of different cellular differentiations and further in predicting CA4P therapeutic efficacy in primary HCCs and intrahepatic
metastases.