Accumulation of immunoglobulin G at focal sites of inflammation

Abstract

To evaluate the factors responsible for the accumulation of indium-111 immunoglobulin G (111In-IgG) at sites of inflammation, sequential measurements of tissue blood volume, interstitial fluid volume and accumulation of radiolabelled albumin and IgG were made in rats following Escherichia coli infection in the thigh. Compared with normal thigh muscle, there was approximately two-fold increase in interstitial fluid volume and approximately 1.5-fold increase in plasma and red blood cell volumes in infected muscle. For both proteins, there was a fivefold increase in influx rate constant (kin) in infected muscle. In normal muscle, the interstitial fluid concentration of labelled human serum albumin (111In-HSA) was significantly higher than that of 111In-IgG (P less than 0.01). In contrast, the concentrations in infected muscle were nearly identical. The concentration ratios (infected to normal muscle) were 1.7:1 for HSA and 3:1 for IgG. These data suggest that the infection imaging properties of 111In-IgG are related to expansion of the space available to macromolecules in infected tissue and increased transport into this space. At clinically important imaging times (24-48 h after injection), the higher target-to-background ratio of 111In-IgG compared with 111In-HSA is not due to the higher accumulation IgG in infected tissue but rather to the higher accumulation of HSA in normal tissue.