Applications of Accelerator Mass Spectrometry to therapeutic proteins 2: target mediated disposition

Published: 10 September, 2012
Author: Graham Lappin, Tracey Oxley, Mark Seymour and Joseph Balthasar

Poster presented at the 11th International Symposium on the Synthesis and Applications of Isotopes and Isotopically Labelled Compounds (IIS 2012) in Heidelberg, 9-13 September, 2012.It was shown in a previous study that the plasma clearance of T84.66 (anti-carcinoembryonic antigen, CEA) in a xenograft mouse model can be used to test for the presence of CEA as a marker for tumor presence. T84.66 was labeled with 125I and administered in a sufficiently low dose as not to saturate the CEA antigen, to four groups of mice consisting of a control and 3 tumor volumes.

The study demonstrated the application of a pharmacokinetic test, based on the concept of target-mediated drug disposition, to quantitatively detect colorectal tumor xenografts in mice. Transferring the technique into humans is problematic because of the low doses of antibody required and the potential radioactive burden required to achieve sufficient assay sensitivity. As an alternative to 125I, the study was in part repeated using T84.66 labeled with 14C and the ultra-sensitive isotope ratio technique of accelerator mass spectrometry (AMS) used for the analysis.

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