Chapter 7: Standard Biological and in vivo Methods

MRI contrast agent development requires knowledge of organic and inorganic chemistry to produce probes of high signal-generating capability. However, chemistry alone is insufficient to create the most effective and safest agents, and many promising candidates show properties in test tubes that never translate to in vivo applications. The effective development of contrast agents requires study and keen understanding of their effects on biological targets, including targeted cells or biomarkers, and bystander cells, such as in the clearance pathways. This chapter further details the importance of in vitro profiles of contrast agents for optimization of biotolerance and image-enhancement capabilities that are needed before in vivo investigations are performed. In this chapter, a number of in vitro assessments of MRI contrast agent behavior for cytotoxicity, cell binding, and cell uptake are discussed. This is followed by a description of distribution, metabolism, and pharmacokinetics, which are critical to interpreting in vivo imaging studies. Finally, practical aspects of contrast-enhanced preclinical MRI with regard to molecular probes and imaging are considered.