Biodistribution and Catabolism of Ga-67-Labeled Anti-Tac dsFv Fragment

The disulfide-linked fragment (dsFv) of the antibody to the α subunit of the IL2 receptor has been radiolabeled with a [Ga-67] Ga-2-(p-SCN-Bz)-NOTA derivative linked through an isothiocyanato group to either the e-amino group of lysine or the α-amino group of the N-terminal amino acids. This low molecular weight protein (LMWP) has been proposed as a tumor diagnostic agent. However, >60% of the injected dose localized in the mouse kidney. The major catabolites (>95%) in the kidney were identified as the Ga-2-(p-SCN-Bz)-NOTA conjugate with either lysine or methionine, with no evidence of transchelation of Ga-67. Since different amino acids in the dsFv were radiolabeled according to this procedure, it was possible to study the relative residence times of the various catabolites. The methionine conjugate had a significantly shorter residence time than the lysine conjugate in the same kidney. Labeling the appropriate amino acid in a LMWP may lead to reduced residence times and increased diagnostic or therapeut...