Nanobody-loaded and -coated microbubbles: a tool for drug delivery and molecular imaging

Student thesis: Doctoral Thesis

Abstract

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
Date of Award29 Sep 2011
Original languageEnglish
Awarding Institution
  • Vrije Universiteit Brussel
SupervisorTony Lahoutte (Promotor), Bernard Cosyns (Co-promotor), Nick Devoogdt (Co-promotor), Hendrik Everaert (Jury), Stephane Carlier (Jury), Steve Schoonooghe (Jury), Niek Sanders (Jury), Luc Pierard (Jury) & David Glover (Jury)

Keywords

  • molecular imaging
  • ultrasound contrast agents
  • nanobodies

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