Biodistribution and catabolism of Ga-67-labeled anti-Tac dsFv fragment.
The disulfide-linked fragment (dsFv) of the antibody to the alpha 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 epsilon-amino group of lysine or the alpha-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 therapeutic ratios.
Wu
C
C
Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Jagoda
E
E
Brechbiel
M
M
Webber
K O
KO
Pastan
I
I
Gansow
O
O
Eckelman
W C
WC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D005710:Gallium Radioisotopes; D006801:Humans; D007128:Immunoglobulin Fragments / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D005710:Gallium Radioisotopes; D007128:Immunoglobulin Fragments; D015375:Receptors, Interleukin-2; C055966:immunoglobulin Fv