Ph.D. and M.D. researchers with an interest in molecular imaging concepts, applications and clinical translation.

- Review basics of paramagnetic relaxation theory

- Define r₁ and r₂ relaxivity

- Discuss factors important to design of relaxation based contrast agents

- Understand properties of T₁, T₂* relaxation agents for in vivo use

- Illustrate examples of clinical relaxation based contrast agents

- Illustrate examples of novel targeted relaxation based contrast agents

MRI can be enhanced by the use of contrast agents that enable better delineation of the abnormal tissue from its surroundings and these are now used in the clinic for routine examination of pathologies, particularly cancer. This lecture discusses targeted ¹H MRI contrast agents for application in cancer imaging. We begin with an introduction to MRI and the mechanism of MRI contrast agents. We then classify the contrast agents for ¹H MRI into two categories namely the “positive” contrast agents (appearing bright on MR images) and the “negative” contrast agents (appearing dark on MR images) and discuss the general properties that affect the sensitivity as well as applications. Gd-based agents typically belong to the class of positive contrast agents. These produce a high intensity on T₁-weighted images by shortening of T₁ relaxation times. Negative contrast agents are typically nanoparticles consisting of a crystalline iron oxide core and a shell. These agents produce predominantly local field inhomogeneities resulting in very high T₂ and T₂* relaxivities. Contrast agents can also be classified based on size and structure: small-molecular, macromolecular, micellar, liposomal and nanoparticulate and the differences between these will be illustrated. Small molecular agents (linear or macrocyclic) are usually injected intravenously and tend to distribute in the plasma and interstitial spaces. The agents have a half-life of 1-2 hr and are cleared through the renal route. The pharmacokinetics and route of excretion of these agents can be modified by chemical alteration of the chelates. Conjugation of the small molecular Gd chelates with macromolecules such as polymers, dendrimers and proteins improves the relaxivity of contrast agents by various mechanisms. Macro-molecular and nanoparticulate contrast agents have been shown to have higher relaxivities, longer blood circulation, better accumulation in tumor tissues, longer retention times (due to slower clearance) and lower toxicities than small molecular agents. Contrast agent retention in pathological tissues can be further improved by incorporating chemical moieties that “target” the tissue microenvironment. Finally we outline the future prospects for this important field of research and highlight some new applications of relaxation based agents (e.g. hypoxia imaging).