NMR imaging is a well-established technology for obtaining cross-secti
onal anatomic pictures of organs and tissues. In addition, NMR can pro
vide valuable information about the physiologic state of organs and ti
ssues, especially, as a consequence of cellular injury. With this in m
ind, NMR in combination with gadolinium-based contrast enhancing agent
s has been used to assist in the detection of abnormalities to joints
as well as to evaluate the status of damage resulting from an injury t
o this site. We describe the synthesis of a new nitroxide, which is bi
oresistant to the one-electron reduction mediated by superoxide in the
presence of cysteine. This model mimics the reduction of nitroxides b
y extracellular secretion of superoxide by PMA-stimulated neutrophils.
With this nitroxide, we found, in the range from 15 to 17.5 mu moles,
enhancement of an NMR image in the knee joint of rabbits. Of interest
is the finding that the contrast image remained for at least 90 minut
es. These results demonstrate the utility of nitroxides as contrast en
hancing agents for NMR imaging of joints.