Imaging Voltage Gated Sodium Channels Using Positron Emission Tomography

Informazioni relative al progetto

INSCAPE

ID dell’accordo di sovvenzione: 656644

DOI

10.3030/656644

Progetto concluso il 5 Maggio 2018

Data della firma CE 23 Aprile 2015

Data di avvio 15 Maggio 2015

Data di completamento 14 Maggio 2018

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 239 860,80

Contributo UE

€ 239 860,80

Coordinato da

KLINIKUM DER UNIVERSITAET ZU KOELN
Germany

Periodic Reporting for period 2 - INSCAPE (Imaging Voltage Gated Sodium Channels Using Positron Emission Tomography)

Periodo di rendicontazione: 2017-05-15 al 2018-05-14

Sintesi del contesto e degli obiettivi generali del progetto

In this project, we have developed a novel and unique imaging tool that helps visualizing pivotal physiological processes, which are important for human health, in vivo. In particular, our imaging technology allows extracting information on electrophysiological processes that underlie, for instance, heart beat in a non-invasive way. We believe that this is directly related to important societal challenges since cardiovascular disease is responsible for the majority of all deaths worldwide. Along these lines, we were able to demonstrate the translational potential of our invention for human heart failure, which is a live-threatening condition that currently lacks efficient diagnosis and treatment. Furthermore, we were able to elucidate an unexpected role of pain medication in a poorly understood part of the central nervous system. Finally, we made first steps in identifying additional potential of our new tool for impacting breast cancer diagnosis. Therefore, we can conclude that we have successfully achieve the overall objective of developing a novel translational imaging tool, which potentially improves patient outcomes. Noteworthy, the major indication fields of cardiovascular disease, pain, and cancer represent all-important and critical challenges of societies in Europe and worldwide.
The overall educational objective was to provide training in chemical synthesis, small molecule analytics, radiochemistry, and molecular imaging to the researcher. These training goals were efficiently achieved by the mentorship and hands-on training at the partner institutions as well as attendance to educational workshops.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

Chemical Synthesis and Design:
The molecular basis for achieving our overall objective of imaging voltage gated sodium channels (NaVs) with positron emission tomography (PET) was the organic synthesis of small molecules binders, and precursor molecules for radioactive labeling with the clinically relevant isotope 18F. In addition to assembling a small library of molecular candidates, this work also included establishing purification protocols for HPLC and investigation of different labeling methodologies. The main result was the design of new imaging probes and a reliable and efficient chemical and radiochemical protocol granting access to these novel entities, which allowed us to proceed to the next project stage.

Autoradiography and Molecular Imaging:
With potential imaging probes in hand, we proceeded to test their ability to visualize NaVs in primary tissue by autoradiography (AR). After successfully identifying the most powerful tool, we further investigated ligand binding kinetics and found highly advantageous properties. Subsequently, the imaging probe was applied for non-invasive in vivo imaging by means of small animal PET. The major result was successfully demonstrating the ability of our unique and novel imaging tool to visualize NaVs in vivo. Motivated by this ground-breaking achievement,we further investigated the translational potential of our imaging technology and confirmed applicability to human tissue and large animal imaging.

Exploitation and dissemination:
These results were the basis of a patent application, which preceded a peer-reviewed publication and a presentation at a conference.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

This project provided major progress beyond the state of the art by establishing the first PET imaging probe for NaVs. As such, we have developed a platform technology, which can impact all-important human diseases including cardiovascular disease, malfunction of the central nervous system, and cancer.
This impactful scientific progress translated into major positive career impact for the researcher in conjunction with the achieved training goals. Most importantly, the researcher has been offered a position as assistant professor in a tenure track program at a European university, which he accepted during the action.

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