NVLS-LFA-1

There is a critical need for imaging probes with molecular specificity for in vivo imaging of inflammation and activation of immune cells. These probes will have clinical utility in the early diagnosis and monitoring of inflammation, infection, and tissue response to targeted drug therapy. Currently, the options for functional clinical imaging of inflammation and infection employ radiopharmaceuticals such as 67Ga-citrate, 111In-leukocytes, and 18F-fludeoxyglucose that localize based upon the detection of mass infection or general metabolic activity, lacking specificity for molecular events associated with inflammation and immune cell activation.

The LFA1-targeted molecular imaging probes being developed will be useful for broad applications assessing inflammation in many tissues induced by a variety of naturally occurring and man-made infectious agents and nanomaterials. These molecular imaging probes may prove useful for non-invasive monitoring of the in situ pathogenesis, disease progression, and tissue response to interventions of many diseases that are accompanied by acute and chronic inflammation. Further, these probes will enable the in vivo clinical evaluation of a wide variety of anti-inflammatory therapeutic strategies.

In 2005, the misdiagnosis of appendicitis cases is estimated to cost $2.4 billion each year in the United States. Appendicitis is a common condition in the United States, with an estimated 350,000 hospital inpatient cases per year. The rates of perforation and negative appendectomy have remained stable since 1998, despite the emergence of computed axial tomography or CT in the diagnosis of appendicitis. Each year in United States, over 38,000 inpatients undergo unnecessary appendectomies resulting in hospital charges of over $1 billion. As many as one in ten appendectomies, one in five elderly patients, are found to have a normal appendix. Over 100,000 patients annually suffer a perforated appendix resulting in additional hospital charges of over $1.2 billion. Overall, 29% of all appendectomies and 50% of those performed in the elderly patients will have a perforated appendix resulting in more than twice the hospital charges and average length of hospitalization compared to those with uncomplicated appendicitis. Earlier, more accurate diagnosis of appendicitis would result in substantial clinical and economic benefits.