PROJECT SUMMARY
Magnetic resonance imaging (MRI) is a non-invasive imaging technique that can provide
information on the anatomy, function, and metabolism of tissues in vivo. MRI scans make use of
the two hydrogen atoms in water to generate the image. Unfortunately, the intrinsic contrast
provided by the water T1 and T2 relaxation times, and changes in their values brought about by
tissue pathology, are often too limited to enable a sensitive and specific diagnosis. For that
reason, increasing use is made of MRI contrast agents that alter the image contrast following
intravenous injection. Depending on the chemical composition, molecular structure, and overall
size of the contrast agents, the in vivo distribution volume and pharmacokinetic properties vary
widely with little control, and this largely determines their use in specific diagnostic tests.
Additionally, traditional gadolinium-based contrast agents have been implicated as potential
nephrotoxins and neurotoxins. To overcome these limitations the proposed research will focus on
designing dynamic, activatable, or ‘intelligent’ MRI contrast agents based on iron(II) complexes
that undergo thermally induced spin-state crossover to provide local temperature data and tissue
contrast. These novel contrast agents will allow for the monitoring of tissue environments with
greater spatial and temporal data feedback. The complexes will also allow for enhanced signal
resolution at therapeutically relevant temperatures for patients undergoing high-temperature
tumor ablation. We will design Fe(II) crossover complexes that can exist in an ‘on’ or ‘off’ state
depending on the local temperature of their physiological environment, providing an added layer
of detail in real-time MRI scans. Additionally, we propose attaching these contrast agents to
known peptide binders for discrete tissue types or cell and protein receptors. The ability to target
specific tissue types and direct accumulation of these contrast agents would enhance imaging
and lead to greater patient outcomes. The proposed research will also have a tremendous positive
impact on the research environment at Salisbury University through the engagement of
undergraduate students in research projects at the forefront of synthesis of MRI contrast agents,
likely propelling them to future careers in the chemical and biomedical sciences.