MRI contrast enhancement of necrosis by MP-2269 and gadophrin-2 in a rat model of liver infarction.
OBJECTIVE
The mechanisms of action leading to specific localization of necrosis-avid contrast agents (NACAs) such as gadophrin-2 are not well defined. It has been suggested recently that agents with a high degree of serum albumin binding may also serve as NACAs by virtue of nonspecific hydrophobic interactions. The present MRI-histomorphology correlation study was conducted to verify the likelihood of the proposed albumin-binding mechanism by comparing an albumin-binding blood pool agent, MP-2269, with gadophrin-2 in a rat model of reperfused liver infarction.


METHODS
Reperfused infarction in the right liver lobe was surgically induced in six rats. Serial T1-weighted MRI was performed before and after intravenous injection of MP-2269 at 0.05 mmol/kg and repeated in the same rats 24 hours later after intravenous injection of gadophrin-2 at the same dosage (0.05 mmol/kg). The MR images were matched with corresponding histomorphological findings. The signal intensity and contrast ratio of infarcted and normal hepatic lobes were quantified and compared between the two agents during the postcontrast course.


RESULTS
Before contrast, the infarcted lobe was indiscernible from normal liver on T1-weighted MRI. Shortly after injection of both MP-2269 and gadophrin-2, a negative contrast occurred between infarcted and normal liver because of a strong liver signal intensity enhancement and an inferior uptake in the necrotic liver. On delayed phase (>60 minutes), a necrosis-specific contrast enhancement (contrast ratio 1.6) developed with gadophrin-2 but not with MP-2269. The MR images matched well with corresponding histomorphological findings.


CONCLUSIONS
Although both MP-2269 and gadophrin-2 feature an albumin-binding capacity, only gadophrin-2 displayed a persistent necrosis-specific contrast enhancement in the rat model of reperfused liver infarction. Therefore, the role of albumin binding in the mechanisms of NACAs should be reevaluated.
Department of Radiology, University Hospitals, Catholic University of Leuven, Belgium. Yicheng.Ni@med.kuleuven.ac.be
Y
Y
Ni
K
K
Adzamli
Y
Y
Miao
E
E
Cresens
J
J
Yu
M P
MP
Periasamy
M D
MD
Adams
G
G
Marchal
D000818:Animals; D003287:Contrast Media; D019786:Gadolinium DTPA / Q000031:analogs & derivatives*; D007238:Infarction / Q000473:pathology*; D008099:Liver / Q000098:blood supply / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008652:Mesoporphyrins; D008665:Metalloporphyrins; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar
D003287:Contrast Media; C112668:MP 2269; D008652:Mesoporphyrins; D008665:Metalloporphyrins; C118579:gadophrin-2; D019786:Gadolinium DTPA