DEGRADATION OF LYOPHILIZED AND RECONSTITUTED MACROSCINT(R) (DTPA-IGG)- PRECIPITATION VS GLUCOSYLATION

Diethylenetriaminepentaacetic anhydride (DTPA) conjugated to IgG (DTPA -IgG) and labeled with In-111 is useful for detecting focal sites of i nfection and inflammation (R.H. Rubin, A.J. Fischman, R.J. Callahan, B . Khaw, F. Keech, M. Ahmad, R. Wilkinson and H.W. Strauss, In-111-labe led nonspecific immunoglobulin scanning in the detection of focal infe ction, N. Engl. J. Med., 321 (1989) 935-940). MACROSCINT(R) contains D TPA-IgG formulated as a lyophile from a citrate buffer containing malt ose. Exposure of both reconstituted and lyophilized MACROSCINT(R) to i ntense light resulted in degradation primarily via formation of precip itating aggregates. However, lyophilized and reconstituted MACROSCINT( R) responded differently to thermal stress. Reconstituted MACROSCINT(R ) subjected to thermal stress (65 degrees C) also degraded through for mation of precipitating aggregates. In contrast, exposure of lyophiliz ed MACROSCINT(R) to thermal stress (65 degrees C) resulted primarily i n an increase in the molecular size of the MACROSCINT(R) DTPA-IgG mono mer. This increase in molecular size was a function of both the moistu re 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. Monosa ccharide analysis of the samples demonstrated that this increase in mo lecular size corresponded to an increase in the amount of glucose cova lently attached to the IgG. These data suggest that the increase in mo lecular size as a function of thermal stress is due to the covalent at tachment of maltose, which is a glucose disaccharide present in the ly ophile as an excipient, to the IgG. This degradation pathway was only observed in the lyophile.