Fluorine magnetic resonance imaging (19F MRI) is a promising technique for non-invasive diagnostic imaging due to the infinite penetration depth of MRI techniques, the favorable MR properties of fluorine atoms and lack of detectable fluorine signals in human body. Inorganic metal complexes are an important class of smart 19F MRI contrast agents for imaging different biological environments and species through changes of metal oxidation state, spin state and coordination environment that modulate fluorine MR signal intensity and/or chemical shift. We have developed a series of fluorinated metal complexes for imaging cellular hypoxia (low O2-tension) based on CuATSM, a Cu2+ scaffold that has been widely explored as a radioactive 60/62/64Cu2+ complex for PET imaging of hypoxia. Combined spectroscopy and electrochemistry studies showed that in the aerobic environment, the complexes remain in its Cu2+ state, in which the paramagnetic Cu2+ center significantly shortens the relaxation times of the fluorine atoms in the complex, affording a fast-relaxed (quenched) 19F MR signal. In the reducing environment, the Cu2+ center of the complexes is reduced to diamagnetic Cu+, thus restoring the quenched 19F signal. Importantly, live cell experiments demonstrated that incubation of cancer cells with synthesized Cu2+ complexes resulted in a selective 19F MR signal enhancement in cells grown under hypoxic conditions versus normal oxygenated conditions, which can be evaluated through 19F NMR and 19F MRI. The above results thus reveal the potential for using fluorinated CuATSM-type complexes as imaging agents for hypoxia in vivo. The relationship between the compound structure and Cu2+-redox potential, Cu2+-relaxation effect and complex lipophilicity will be discussed.

Fluorinated copper scaffolds for 19F MR-based detection of hypoxia

255th National Meeting (2018)

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