Mangafodipir trisodium (MnDPDP)-enhanced magnetic resonance imaging of the liver and pancreas

Detta är en avhandling från Uppsala : Acta Universitatis Upsaliensis

Sammanfattning: Contrast-enhanced magnetic resonance imaging (MRI) of the liver and pancreas is frequently performed to improve the sensitivity and specificity of lesion detection in these organs. The concept of using tissue-specific contrast media is to selectively enhance the normal parenchyma, but not lesions, so that the contrast between tumorous and normal tissue is increased, and lesion detectability improved. Mangafodipir trisodium (MnDPDP) has been developed as a hepatocellular-specific contrast agent, but uptake has also been found in pancreatic tissue. In this study the safety and diagnostic efficacy of MnDPDP were investigated in both healthy volunteers and patients with liver and pancreatic tumors.In healthy volunteers (n=8), dose-dependent enhancement in T1-weighted images was observed in the normal liver and pancreatic parenchyma after infusion of MnDPDP at doses of 5 and 10 μmol/kg. The maximal enhancement in the two dose groups was 77 and 110% in the liver, and 57 and 84% in the pancreas, respectively. The enhancement-over-time profiles demonstrated that the effective imaging window was about 2 h for the liver, and over 4 h for the pancreas. There was no measurable enhancement in brain structures protected by intact blood-brain barrier, and no changes of clinical importance were found in vital signs or in blood and urinary chemistry variables.Compared with unenhanced images (including T2-weighted images), significantly more lesions were detected, on MnDPDP-enhanced T1 images in 82 patients with liver tumors (mostly metastases). Features such as rim enhancement and the enhancement in hepatocellular carcinomas can provide information for differential diagnosis.In a study on patients with pancreatic tumors, mainly adenocarcinomas (n=21) and islet cell tumors (n=19), two additional lesions were found in the MnDPDP-enhanced images. The contrast enhancement in the pancreatic parenchyma can vary greatly, depending on the site of the enhancingpart of the organ in relation to a large tumor. The tumors of both origins were also enhanced post-contrast, but to a lesser degree than the normal pancreatic tissue.MnDPDP enhancement was investigated in 30 liver metastases from endocrine tumors in 13 patients. These lesions showed a signal increase of about 49% post-contrast, which lasted longer than that in the normal liver tissue. The findings may help to distinguish these tumors from other metastatic tumors.T1-weighted sequences of four types, including a spin-echo and three variants of fast gradient-echo sequences, and various parameter combinations, were investigated in healthy volunteers (n=6), with the aim of finding the optimal sequence for MnDPDP-enhanced MRI of the liver andpancreas. The fat-and-water out-of-phase, fast field (gradient)-echo sequence was the best for imaging of both the liver and pancreas.The studies have shown that MnDPDP is safe when given as an infusion and is effective as a liver- and pancreas-specific contrast medium, with improved lesion detection in MRI of these organs. It is also useful for the characterization of liver tumors.

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