Delivery of diagnostic agents for magnetic resonance imaging

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Abstract

A review of contrast agents used for magnetic resonance imaging was made with regard to methods of drug delivery using published literature. Since the clinical approval of Gd-DTPA in 1988, there has been extensive research towards developing organ- and tissue-specific contrast agents. Targeting strategies have consistently improved along with improvements in nuclear medicine imaging, and a broad spectrum of potential agents has accumulated. Liver, blood-pool targeted, and, due to their inherent convenience of delivery, intraorally administered gastrointestinal agents have been developed or are being developed. For intravenous contrast agents, collective magnetic labels with modifications for some specificities results in the larger-sized agents which can be an obstacle for the agent in accessing the targeted cells. In conclusion, the next step in the development of specific contrast agents for clinical use is to improve non-specific delivery to the extra-capillary space adjacent to targeted cells.

Introduction

Contrast agents for magnetic resonance (MR) imaging do not generate signals but instead affect the hydrogen nuclei (mainly water protons), which then generate signals to be imaged. This indirect function of a contrast agent depends not only on its concentration in the tissue but also on its environment, such as the distribution within a voxel on an image, and the density, environment, and movement of protons in the tissue. Thus, an understanding of the basic physics of MR imaging is important for understanding the design of contrast agents for effective delivery. The non-specific extravascular, extracellular contrast agents used for MR imaging are well established and used popularly to date. The next step is the development of organ- and tissue-directed agents with a limited biodistribution. A variety of useful agents that target a specific organ or tissue have been reported. A liver reticuloendothelial system (RES)-directed agent has already been approved clinically, and some agents that target hepatocytes or are distributed in the blood pool are now in clinical trials.

Although this review is restricted mainly to the clinically relevant agents in each class, some preliminary reports of agents with possibilities for new applications are also mentioned to indicate the trend for future research in this field.

Section snippets

General aspects

Because the mechanism of contrast enhancement in MR imaging is different from that of other modalities, there are advantages and disadvantages in the design of contrast agents. In this section, the major principles underlying agent delivery for MR imaging are discussed.

Delivery to specific organs and tissues

Problems in the delivery of MR contrast agents are essentially the same as for the other modalities and might be the same as for therapeutic pharmaceuticals. Although there are several ways to classify the contrast agents, this section focuses on classifying according to the method and mechanism of specific delivery.

Conclusion

The development of contrast agents for MR imaging, to date, has focused on potential application and a broad spectrum of potential agents has been developed with the development of imaging methods. Liver, blood-pool targeted, and intraorally administered gastrointestinal agents have been successfully developed due to the absence of barriers for their delivery. For intravenous agents, however, restricted capillary permeability can impede the delivery of some agents integrated for specificity and

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