Biomarkers discovery

PIs: Prof André Luxen, PhD, Dr David Thonon, PhD, Dr Jérome Paris, PhD, Dr Christian Lemaire, PhD, Dr Alain Plenevaux, PhD

Introduction

To characterize and measure biological process at the cellular and molecular level, molecular imaging requires two elements:

  1.  A molecular probe whose concentration and/or spectral properties are altered by the biological process investigated
  2. An imaging system able to monitor the probe in vivo

Today only Positron Emission Tomography (PET) has the sensitivity to visualize molecular process in a volume and target-depth independent manner, and in three dimensions. Therefore, the real challenge is the development of new specific molecular PET probes.

One of the main challenges in the development of PET tracer is to introduce the signaling component (typically a short half-life radioisotope like fluorine-18) onto the affinity component (a biomolecule specific to the biological process studied)

Radiosynthesis of molecular probes

Our laboratory has an experience of more than 25 years (verif) in the radiochemistry of PET tracer. Work accomplished at the Cyclotron Research Centre has considerably impacted the way in which PET tracer are daily prepared in the entire world. By example, we introduced the use of solid phase extraction cartridges (Sep-Pak) for purification of PET tracers. Our laboratory was also at the origin of the development of the first FDG automated radiosynthesizer (coincidence module). Nowadays, Liège is a major place in this field with two societies active (TRASIS and GE Healthcare-MDX PET Chemistry Systems).

Our team still works to develop faster, cheaper and safer methods to prepare PET tracers.

For example, we have developed and patented more convenient methods to introduce fluorine-18[1] on organic compounds.  Thanks to these technical developments, we are now able to produce an increasing number of high quality fluorine-18 based tracers suitable for clinical studies (GMP facilities).

Some recent molecular imaging developments require more elaborated compounds. (e.g. peptides, proteins, oligonucleotides, lipids, …) where stability issues and side reactions prevent their direct radiolabeling

In order to tackle this problem, we have developed a library of small fluorine-18 labeled compounds (prosthetic groups) which can be easily conjugated to biomolecules specific to the biological process studied.

Applications of targeted molecular probes at the Liège Cyclotron Research Centre

1. Fundamental studies: understanding disease and biological process

We provide several radioligands dedicated to the PET investigation of brain receptors. These studies permit a better understanding of various brain disorders like Parkinson disease or addiction, … In fine, these investigations will help defining better treatment and handling of patients.

2. Tool for drug development (proof of targets, mechanism, efficacy, pharmacokinetics, biodistribution)

Positron Emission Tomography (PET) is gaining increased importance in the field of drug development as a powerful in vivo pharmacological imaging modality. This high sensitivity technique (picomolar levels) is particularly well suited to collect quantitative and dynamic biodistribution data (eg. Microdosing studies) at an early stage of clinical development of a new drug, as well as to carry out detailed drug occupancy studies.

For this, we currently collaborate with various pharmaceutical companies to label lead compounds. In vivo PET imaging with these candidates will help to select the best one for clinical trials

3. Diagnostic radiopharmaceuticals (“predisease states”, monitoring of therapy)

We produce various PET tracers related to oncology and neurodegenerative diseases under GMP conditions.

 


[1] Fluorine-18 is by far the most used positron emitting radionuclide in PET thanks to its physical and nuclear properties. 





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