Molecular imaging of atherosclerotic plaque inflammation using nanobodies: paving the path towards clinical translation.

Scriptie/masterproef: Doctoral Thesis

Uittreksel

In the recent years, important advancements have been achieved in atherosclerosis research by elucidating the molecular and cellular pathways of inflammation that trigger the thrombotic complications of atherosclerosis. Translating of these findings has stimulated the development of new multi-modal imaging modalities incorporating molecular probes to provide detailed information involving atherosclerosis plaque structure and inflammation.
The aim of this thesis was to optimize and investigate the potential of small antigen fragments called nanobodies as nuclear imaging agents to target atherosclerosis plaque inflammation as a step towards clinical translation.
In the first part of the thesis we have described the development and validation of a nanobody based molecular probe for PET/CT imaging of vascular cell adhesion molecule-1 (VCAM-1) expression as a marker of plaque inflammation. We have shown that 18F-radiolabeld anti-VCAM-1 nanobody is a specific tracer that accumulates in atherosclerotic lesions.
In the second part of the thesis, we have demonstrated that anti-VCAM-1 nanobody can be radiolabeled with radiometals, such as 68Ga as an alternative strategy that is easy to implement in clinical routine.
In the third part of the thesis we have investigated the feasibility of imaging the presence of alternatively activated macrophages by targeting macrophage mannose receptor (MMR) expression in a murine model of atherosclerosis. In this particular animal model, we didn’t find a correlation between tracer uptake and plaque burden because of the intraplaque absence of MMR expression.
Datum Prijs25 apr 2019
TaalEnglish
Toekennende instantie
  • Vrije Universiteit Brussel
BegeleiderSophie Hernot (Promotor), Bernard Cosyns (Promotor), Steven Droogmans (Co-promotor), Christian Vanhove (Co-promotor), Danilo Neglia (Jury), Paul Vermeersch (Jury), Marleen Keyaerts (Jury), Juan Antonio Sieira Rodriguez-Moret (Jury), Kaoru Tanaka (Jury) & Ramses Forsyth (Jury)

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