Biodistribution and catabolism of Ga-67-labeled anti-Tac dsFv fragment

Bioconjugate Chemistry
C WuWilliam C Eckelman

Abstract

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.

Citations

Jun 5, 2002·Annals of Nuclear Medicine·Yasushi Arano
Jun 6, 2000·Advanced Drug Delivery Reviews·Y Arano
May 30, 2008·Advanced Drug Delivery Reviews·Hiromichi AkizawaYasushi Arano
Feb 5, 2005·Nuclear Medicine and Biology·C Andrew BoswellCarolyn J Anderson
Sep 11, 2018·Medical Physics·Abner D SoaresAlessandro Facure
Apr 19, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tomoya UeharaYasushi Arano
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Aug 10, 2010·Journal of Medicinal Chemistry·Lathika HoigebazarYoung Keun Chung

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