CMR2009: 3.05: Diffusion‐weighted MR imaging of pancreas using manganese oral contrast agent

Abstract

Conclusions: Considering the signal enhancement of normal liver parenchyma and the improved liver-lesion contrast, our initial results suggest that the optimal time point for liver MR imaging is between 2 and 6 h after oral intake of CMC-001. Rationale and Objectives: The limited sensitivity of MRI is the major drawback to the thorough involvement of this modality in Molecular Imaging applications. Some years ago the use of Gd-loaded apoferritin was reported (1) with a relaxivity of ca 600-800 mM À1 s À1. The attainable relaxation enhancement of Gd-loaded apoferritin is limited by the number of Gd-HPDO3A (<10) that it is possible to entrap in the inner cavity. It has been reported that metal ions, as well as iron, can be stored in high number inside the apoferritin cavity. Among them it has been shown that manganese ions enter the protein to yield wellcharacterized nanosized crystals of b-MnOOH (2). However, to improve T 1 -relaxation enhancement capabilities it is necessary to solubilize the metal ion payload inside the inner cavity. The dissolution of b-MnOOH occurs via the reduction of Mn(III) to Mn(II) operated with aminopolycarboxilic acids that also act as coordination ligands for sequestering weakly coordinated manganese ions on the outer surface of the protein.Methods: Iron-free horse spleen apoferritin was reconstituted in the presence of MnCl 2 solution at pH¼9 under air. After a 1 week reaction time, the samples were treated with aminopolycarboxilic acids (NTA, TETA), which resulted the elimination of bound Mn ions from the external surface of the protein and the reduction of the internally loaded Mn(III) to Mn(II). Results: The reductive treatment has allowed generation of an apoferritin-based nanocarrier (Mn-Apo) containing up to 300-400 Mn(II) aqua ions encapsulated in the inner cavity. This yielded the remarkable relaxivity value (per apoferritin) of ca 4000-7000 mM À1 s À1. Mn-Apo formed by endogeneously occuring molecules and ions displays a high biocompatibility. It targets hepatocytes with high efficiency and is able to discriminate healthy cells from hepatocarcinoma ones, on the basis of the different expression of ferritin receptors. Mn-apo was injected into C57BL/6 mice at a dose of 0.01 mmol kg À1 of Mn, and a very high signal intensity (SI) enhancement of the liver in the MRI images was detected 30 min and 1 h after the administration. Complete elimination of the probe occurred 24 h after the decreased liver SI. Conclusion: Mn-loaded apoferritin is a very efficient probe specific for liver imaging. In particular, it could be useful in the diagnosis of a variety of liver diseases involving differences in the hepatic iron storing capabilities. Purpose: The purpose of this study was to evaluate visual appearance of diffusion-weighted imaging (DWI) using oral manganese contrast agent. Material and Methods: Preliminary study included imaging evaluation of pancreas head with DWI with or without the oral manganese-based contrast agent (Bothdel: 36 mg manganese chloride tetrahydrate, Kyowa Kirin,...