Imaging infection/inflammations. Pathophysiologic basis and radiopharmaceuticals

Inflammation is a localized reaction in the microcirculation that is characterized by fluid and leukocyte transport from the blood into the extracellular tissues. The increase in blood flow and loss of endothelial integrity at the site are particularly important in radiopharmaceutical delivery. This alteration of the microvasculature is probably the earliest response to tissue injury. Within hours of inflammation initiation, the site is invaded with large numbers of polymorphonuclear leukocytes (PMN). These cells are led to the site by various chemo-attractants and are able to concentrate in the blood vessels near the inflammation. Upregulation of three families of adhesion molecules, such as the integrins, immunoglobulin supergene and selectins on both the PMN and endothelial cells is an essential component of this process. While both 111In and 99mTc labeled WBC have had undisputed success in detecting infections and inflammations but there are significant limitations. Because of these limitations there have been many attempts to develop new agents which have primarily targeted PMN. The radioactive agent can either bind to the PMN present at the site or be carried to the site bound to PMN. These targets can be PMN-associated antigens or receptors on an activated PMN. Four monoclonal antibodies, CEA-47, BW 250/183, IMMU-NN3 and MCA-480 have been examined extensively for abscess/infection detection in humans.