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Nanobody-Loaded and –Coated Microbubbles : A Tool for Drug Delivery and Molecular Imaging

Thursday, 29 September, 2011 - 17:00
Campus: Brussels Health Campus
Faculty: Medicine and Pharmacy
auditorium 3
Sophie Hernot
phd defence

Many publications have demonstrated that
ultrasound contrast agents or microbubbles (μBs)
became indispensable tools for functional and
molecular imaging. Additionally, μBs can act as
drug delivery systems, where drug delivery is
triggered by ultrasound. The aim of this thesis is
to develop μBs for targeted drug delivery and
molecular imaging by making use of small
antigen binding fragments called nanobodies. In
the first part, we will investigate the bio-effects
caused by ultrasound-mediated μB destruction.
More specifically, we will evaluate in a rat model
the impact of these effects on perfusion and
function of the heart using a technique called
pinhole-gated SPECT. Secondly, as μBs
themselves have been proposed as drug delivery
vehicle, we will design polymeric μBs that allow
loading of nanobodies in order to improve the
pharmacokinetics of the nanobody. These μBs will
be characterized and evaluated for ultrasoundtriggered
drug release. Next, we will focus on the
molecular targeting of the vascular cell adhesion
molecule VCAM-1, a marker of inflamed
endothelium. Hereto, nanobodies will be
generated against this target. The application of
radioloabeled anti-VCAM-1 nanobodies for the
noninvasive imaging of atherosclerosis will be
studied in vivo and a lead compound will then be
selected for further experiments. Finally, by
coupling the selected lead nanobody to the
surface of μBs, VCAM-1 targeted-μBs will be
designed and characterized. This system will in
the end be evaluated in vivo for the molecular
imaging of VCAM-1 expression with ultrasound.

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