Imaging infection/inflammations - Pathophysiologic basis and radiopharmaceuticals

Inflammation is a localized reaction in the microcirculation that is charac terized by fluid and leukocyte transport from the blood into the extracellu lar tissues. The increase in blood flow and loss of endothelial integrity a t the site are particularly important in radiopharmaceutical delivery. This alteration of the microvasculature Is probably the earliest response to ti ssue injury. Within hours of inflammation initiation, the site is invaded w ith large numbers of polymorphonuclear leukocytes (PMN). These cells are le d to the site by various chemo-attractants and are able to concentrate in t he blood vessels near the inflammation. Upregulation of three families of a dhesion molecules, such as the integrins, immunoglobulin supergene and sele ctins on both the PMN and endothelial cells is an essential component of th is process. While both In-111 and Tc-99m labeled WBC have had undisputed su ccess hi detecting infections and inflammations but there are significant l imitations. Because of these limitations there have been many attempts to d evelop 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 bo und to WIN. These targets can be WIN-associated antigens or receptors on at l activated PMN. Four monoclonal antibodies. CEA-47. BW 250/183, IMMU-NN3 a nd MCA-480 have been examined extensively for abscess/infection detection i n humans.