Metabolic Diseases

Development of new radiotracers to assess functional pancreatic β-cell mass by nuclear imaging

The key function of pancreatic β cells is to secrete insulin in response to rising blood glucose levels. These cells are clustered within the islets of Langerhans, which make up only 1 to 2% of the total pancreatic mass and are widely dispersed throughout the exocrine tissue. 
A reduction in pancreatic β-cell mass (BCM), whether anatomical or functional, is a common feature of both T1D and T2D. The ability to assess BCM in vivo would enable clinicians to evaluate and monitor the anatomical and functional status of the patient’s pancreas and ajust treatment accordingly. Furthermore, with advances in β-cell transplantation for the treatment of T1D, there is a growing need for imaging tools that can monitor graft function. 
In research, such imaging tools would also support the evaluation of new therapeutic strategies. Although various techniques have been explored, including MRI, PET or SPECT, none has yet reached clinical application. 

This project aims to develop a new β-cell specific radiotracer suitable for routine use in nuclear medicine, capable to quantify/measure functional mass in vivo via nuclear imaging.
 

Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is usually asymptomatic, at least until advanced/later stages. As a result, the disease often progresses silently, leading ultimately to cirrhosis and/or hepatocellular carcinoma. It is characterized by the excessive accumulation of lipids in the liver and includes a wide spectrum of liver damage, ranging from simple steatosis to steatohepatitis (MASH), which affects about/approximately one third of MASLD patients. 
Unlike simple steatosis, MASH is associated with a poorer prognosis in the long term/run, progressive fibrosis and an increased cardiovascular risk. MASLD is a growing public health concern, strongly linked to obesity. Despite its high and rising prevalence, there is currently no effective non-invasive method to diagnose early-stage disease, and no approved treatment exists.

This project aims to develop and validate a non-invasive nuclear imaging method/technique to detect early markers of the disease/MASLD, in particular inflammation.

Highlights

Nachit M, Montemagno C, Clerc R, Ahmadi M, Briand F, Bacot S, Devoogdt N, Serdjebi C, Ghezzi C, Sulpice T, Broisat A, Leclercq IA, Perret P. Molecular imaging of liver inflammation using an anti-VCAM-1 nanobody. Nat Commun 14(1):1062, 2023. https://www.nature.com/articles/s41467-023-36776-7

A license agreement was granted by UGA (Université Grenoble Alpes) and VUB (Vrije Universiteit Brussel) to develop the application of the cAbVCAM1-5 nanobody in MASLD. 

Cellular senescence is a permanent state of cell cycle arrest, associated with metabolic dysregulation, macromolecular damage, and the acquisition of a pro-inflammatory secretory phenotype. These alterations can lead to a loss of tissue function. Senescent cells contribute to/play a role in many chronic diseases, including metabolic liver diseases and heart failure.
Senotherapies, which are treatments designed to target senescent cells specifically, offer an innovative therapeutic approach with a wide range of potential applications for age-related and chronic conditions. However, evaluating these agents and, in the longer term, monitoring treatment response remain challenging due to the lack of reliable methods to detect and measure senescent cell burden in vivo.

In response to this challenge, a project at the LRB aims to develop a molecular imaging agent capable of visualizing senescent cell burden non-invasively.