Responsive paramagnetic chemical exchange saturation transfer MRI contrast agents

Molecular imaging research has shown great potential to assess the molecular compositions of tissues and provide critical information for clinical diagnoses [1]. These noninvasive assessments of molecular compositions may provide earlier diagnoses of pathologies, may predict therapeutic effects before the therapy is initiated and may provide earlier assessments of therapeutic effects soon after initiating therapy. These molecular-level diagnoses could lead to personalized medicine by tailoring the type, dosage and timing of treatment for each individual patient’s molecular composition. Some molecular imaging methods are routinely used in the clinic, including PET imaging that monitors glucose metabolism [2] and optical imaging that monitors blood oxygenation levels [3]. The strong need for molecular-level diagnoses and these emerging clinical examples have driven explosive growth in molecular imaging research during the last decade. MRI initially contributed to the field of molecular imaging through the development of magnetic resonance spectroscopy and spectroscopic imaging (MRS/I) [4,5]. The unique magnetic resonance frequencies of H, C, F and P atoms within metabolites and drug molecules provide a ‘fingerprint’ that can be used to identify, localize and measure the relative amounts of metabolites and drugs in normal and pathological tissues. These fingerprints provide outstanding specificity for diagnosing metabolic compositions, but the relatively poor detection sensitivity of MRS/I has limited the impact of this method in the clinic. MRI has also contributed to molecular imaging research by developing exogenous contrast agents that accelerate the relaxation, or ‘returnto-equilibrium’, of excited magnetism from