Fluorescently labelled vedolizumab to visualise drug distribution and mucosal target cells in inflammatory bowel disease

ABSTRACT

Objective

Improving patient selection and development of biological therapies such as vedolizumab in IBD requires a thorough understanding of the mechanism of action and target binding, thereby providing individualised treatment strategies. We aimed to visualise the macroscopic and microscopic distribution of intravenous injected fluorescently labelled vedolizumab, vedo- 800CW, and identify its target cells using fluorescence molecular imaging (FMI).

Design

Forty three FMI procedures were performed, which consisted of macroscopic in vivo assessment during endoscopy, followed by macroscopic and microscopic ex vivo imaging. In phase A, patients received an intravenous dose of 4.5 mg, 15 mg vedo800CW or no tracer prior to endoscopy. In phase B, patients received 15 mg vedo- 800CW preceded by an unlabelled (sub)therapeutic dose of vedolizumab.

Results

FMI quantification showed a dose- dependent increase in vedo- 800CW fluorescence intensity in inflamed tissues, with 15 mg (153.7 au (132.3–163.7)) as the most suitable tracer dose compared with 4.5 mg (55.3 au (33.6–78.2)) (p=0.0002). Moreover, the fluorescence signal decreased by 61% when vedo800CW was administered after a therapeutic dose of unlabelled vedolizumab, suggesting target saturation in the inflamed tissue. Fluorescence microscopy and immunostaining showed that vedolizumab penetrated the inflamed mucosa and was associated with several immune cell types, most prominently with plasma cells.

Conclusion

Authors

Ruben Y Gabriëls, Anne M. van der Waaij, Matthijs Linssen, Michael Dobosz, Pia Volkmer, Sumreen Jalal, Dominic Robinson, Marcela A. Hermoso, Marjolijn Lub-de Hooge, Eleonora A.M. Festen, Gursah Kats-Ugurlu, Gerard Dijkstra, Wouter B. Nagengast