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Project

Development of trace substances for in vivo visualization of heat shock protein 90 using positron emission tomography

Heat shock protein-90 (Hsp90) is a ubiquitous "chaperone" protein responsible for the (re)folding of "client" proteins that are thereby stabilized. In tumor cells, both the expression level of Hsp90 and its affinity for Hsp90 inhibitors is significantly increased. Recent research also suggests a role of Hsp90 in neurodegenerative disorders, since Hsp90 also folds and stabilizes client proteins in the brain.

Positron emission tomography (PET) is a molecular imaging technique that allows the dynamic in vivo quantification of the body distribution of radioactive tracers.

We recently reported the development of [11C] NMS-E973, a PET tracer that binds rapidly and persistently to melanoma tumors incubated in mice. This project aims at the development of high-performance fluorine-18 labeled Hsp90 trace substances.

In this project we also aim to identify the molecular form of Hsp90 to which our trace substances bind, using advanced protein identification techniques. In addition, we will also locate the binding sites of the trace substances with subcellular resolution through a combination of fluorescent probes and SPAAC click chemistry.

Furthermore, the role of Hsp90 in different pathologies will be investigated on the basis of PET imaging in laboratory animals.

Date:23 Sep 2019 →  23 Sep 2023
Keywords:Hsp90, PET
Disciplines:Radiopharmacy
Project type:PhD project