Diethylenetriaminepentaacetic
anhydride (
DTPA) conjugated to
IgG (
DTPA-
IgG) and labeled with 111In is useful for detecting focal sites of
infection and
inflammation (R.H. Rubin, A.J. Fischman, R.J. Callahan, B. Khaw, F. Keech, M. Ahmad, R. Wilkinson and H.W. Strauss, 111In-labeled nonspecific
immunoglobulin scanning in the detection of
focal infection, N. Engl. J. Med., 321 (1989) 935-940). MACROSCINT contains
DTPA-
IgG formulated as a lyophile from a
citrate buffer containing
maltose. Exposure of both reconstituted and lyophilized MACROSCINT to intense light resulted in degradation primarily via formation of precipitating aggregates. However, lyophilized and reconstituted MACROSCINT responded differently to thermal stress. Reconstituted MACROSCINT subjected to thermal stress (65 degrees C) also degraded through formation of precipitating aggregates. In contrast, exposure of lyophilized MACROSCINT to thermal stress (65 degrees C) resulted primarily in an increase in the molecular size of the MACROSCINT
DTPA-
IgG monomer. This increase in molecular size was a function of both the moisture content in the vial and the amount of time for which the sample was stressed, but was not a function of the conjugation with
DTPA.
Monosaccharide analysis of the samples demonstrated that this increase in molecular size corresponded to an increase in the amount of
glucose covalently attached to the
IgG. These data suggest that the increase in molecular size as a function of thermal stress is due to the covalent attachment of
maltose, which is a
glucose disaccharide present in the lyophile as an
excipient, to the
IgG. This degradation pathway was only observed in the lyophile.