In Vivo Tumor Uptake of GlyCLICK®-conjugated Antibodies

In collaboration with Minerva Imaging, trastuzumab radiolabeled using site-specific GlyCLICK technology, and produced by random conjugation at lysines, were analyzed using PET/CT imaging to evaluate their performance in vivo. Once chelated, the tracers were labeled with the standard radioisotope Zirconium-89 (⁸⁹Zr) before injection into tumor-bearing mice. Analysis of the injected mice was carried out using PET/CT imaging to measure the biodistribution and tumor uptake of the tracers. The results demonstrate the superior tumor uptake with significantly higher %ID/g and longer circulation time displayed by the site-specific GlyCLICK tracers, as compared to the randomly labeled tracers.

The GlyCLICK conjugated trastuzumab radiolabeled tracers also showed improved ex vivo biodistribution compared to the trastuzumab conjugates prepared by random lysine conjugation. GlyCLICK conjugated antibodies contain a consistent and reproducible number of labels per antibody, with a DOL of 2, compared to a wider and harder to control range of labels per antibody when using the random labelling. This consistent number of labels attached per antibody using the GlyCLICK kit does not only improve performance in vivo, by not impacting the reactive antigen-binding Fab region, but also allows for better quantitation possibilities in PET-imaging experiments.