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Localization of Fc and Fab Fragments of Nonspecific Polyclonal IgG at Focal Sites of Inflammation

Division of Nuclear Medicine, Department of Radiology, and Division of Infectious Diseases, Massachusetts General Hospital
Departments of Radiology and Medicine, Harvard Medical School, Boston, Massachusetts

Correspondence: For reprints contact: Alan J. Fischman, MD, PhD, Division of Nuclear Medicine, Massachusetts General Hospital, Fruit Street, Boston, 02114.

ABSTRACT

Intact IgG, Fc, Fab, and 1/2Fc (reduced and alkylated Fc) were coupled to DTPA, labeled with indium-111 and administered to rats to compare the ability of fragments of IgG to localize at focal sites of inflammation. Two sets of experiments were performed: First, 1, 6, 24, and 48 hr after injection, biodistribution was determined in healthy animals; second, localization at sites of inflammation was determined by scintillation camera imaging of animals with deep-thigh infection due to Escherichia coil. The biodistribution studies demonstrated differences in kidney and liver localization: IgG < Fc < Fab < 1/2Fc (kidney), Fc < 1/2Fc < IgG < Fab (liver). The imaging studies revealed that target-to-background ratio (T/B) and percent residual activity (%RA) for IgG was significantly greater (p < 0.01) than 1/2 Fc or Fab, and T/B for IgG was greater (p < 0.01) than Fc. These studies suggest that the Fc portion of IgG is the fragment with the best imaging properties.