C Sung1, W W van Osdol. 1. Biomedical Engineering and Instrumentation Program, National Center for Research Resources, National Institutes of Health, Bethesda, Maryland, USA.
Abstract
UNLABELLED: Several groups are currently investigating antibody pretargeting as a strategy for improving radionuclide delivery. Pharmacokinetic modeling of these protocols permits analysis of pretargeting protocols under a broad range of possible experimental conditions. METHODS: We used previously developed pharmacokinetic models to predict the temporal uptake and spatial distribution of directly radiolabeled MAb, radiolabeled biotin given after pretargeting with streptavidinylated MAb and radiolabeled streptavidin given after pretargeting with biotinylated MAb in a microscopic, prevascular tumor nodule. Two dose regimens were investigated, as were the effects of internalization and degradation of antibody-antigen complexes (24-hr time constant). RESULTS: Simulations indicate that the protocol involving streptavidinylated MAb and radiolabeled biotin yields higher tumor-to-blood and tumor-to-lung ratios and relative exposures than the other protocols. In the absence of antigen internalization, the peak average molar concentration and MRT of biotin in the tumor nodule is comparable to that of directly radiolabeled MAb, and the spatial distribution of radionuclide is more uniform. When antigen internalization occurs, the peak average concentration and the MRT in the tumor nodule are lower than the corresponding values for directly radiolabeled MAb. CONCLUSION: In the absence of antigen internalization, the protocol involving streptavidinylated MAb and radiolabeled biotin offers pharmacokinetic advantages over the other two protocols.
UNLABELLED: Several groups are currently investigating antibody pretargeting as a strategy for improving radionuclide delivery. Pharmacokinetic modeling of these protocols permits analysis of pretargeting protocols under a broad range of possible experimental conditions. METHODS: We used previously developed pharmacokinetic models to predict the temporal uptake and spatial distribution of directly radiolabeled MAb, radiolabeled biotin given after pretargeting with streptavidinylated MAb and radiolabeled streptavidin given after pretargeting with biotinylated MAb in a microscopic, prevascular tumor nodule. Two dose regimens were investigated, as were the effects of internalization and degradation of antibody-antigen complexes (24-hr time constant). RESULTS: Simulations indicate that the protocol involving streptavidinylated MAb and radiolabeled biotin yields higher tumor-to-blood and tumor-to-lung ratios and relative exposures than the other protocols. In the absence of antigen internalization, the peak average molar concentration and MRT of biotin in the tumor nodule is comparable to that of directly radiolabeled MAb, and the spatial distribution of radionuclide is more uniform. When antigen internalization occurs, the peak average concentration and the MRT in the tumor nodule are lower than the corresponding values for directly radiolabeled MAb. CONCLUSION: In the absence of antigen internalization, the protocol involving streptavidinylated MAb and radiolabeled biotin offers pharmacokinetic advantages over the other two protocols.
Authors: Honor M Rose; Christopher Witte; Federica Rossella; Stefan Klippel; Christian Freund; Leif Schröder Journal: Proc Natl Acad Sci U S A Date: 2014-07-28 Impact factor: 11.205
Authors: Vesa P Hytönen; Olli H Laitinen; Alessandro Grapputo; Anu Kettunen; Janne Savolainen; Nisse Kalkkinen; Ari T Marttila; Henri R Nordlund; Thomas K M Nyholm; Giovanni Paganelli; Markku S Kulomaa Journal: Biochem J Date: 2003-05-15 Impact factor: 3.857