BETAIMAGE

Use of innovative strategies for beta-cell imaging in diabetes mellitus

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 Obiettivo del progetto (Objective)

'The development of sensitive, non-invasive methods for the characterisation and quantification of beta-cell mass would greatly enhance our means for gaining understanding of the pathophysiology of diabetes and allow the development of novel therapies to prevent, halt and reverse the disease. The aim of this project is to develop and apply innovative approaches for beta-cell imaging, the emphasis being on beta-cell mass regulation (loss and neogenesis) with the perspective of entering initial clinical trials. For this purpose, our approach is to: (1) Focus on imaging technologies offering the potential to enter clinical trials during the runtime of the project. Since beta cells contribute only marginally (1-2%) to the total mass of the pancreas, a highly sensitive method for clinical imaging is required. BETA IMAGE will focus on positron emission tomography (PET) relying on chemical resolution, i.e. the specificity of a radiolabelled tracer molecule. The lead compound will be radiolabelled Exendin 4, developed in the consortium for GLP-1 receptor imaging. (2) Devise novel imaging strategies by generating labelled “design” molecules/peptides/nanobody molecules targeting newly identified beta-cell surface proteins. These targets will be identified using a Systems Biology approach. For high-throughput tracer development, a stream-lined methodology will be established based on in vitro model systems and micro-/macroscopic in vivo real time dynamic imaging of tracer distribution by optical coherence tomography and complementary small animal PET and MRI. (3) Build on European excellence in tracer development using peptides, peptide-like and organic molecules for different imaging modalities. To achieve these ambitious goals, we have established a highly interdisciplinary and interactive project combining leading European research groups. In this way, a unique expertise is achieved regarding tracer development and imaging, beta-cells/diabetes and target definition.'

Introduzione (Teaser)

The World Health Organization (WHO) estimates the number of diabetics worldwide to be more than 180 million, with a doubling of this number to be expected by the year 2030. An innovative approach for visualising pancreatic beta cells would contribute to the understanding of disease pathophysiology and enable the assessment of therapeutic interventions.

Descrizione progetto (Article)

Some of the life style-related risk factors for the development of diabetes mellitus are well known, such as obesity in the case of type 2 diabetes (T2D). However, the precise underlying mechanisms leading to the decrease in beta cell mass responsible for the development of impaired glucose tolerance and diabetes still remain to be elucidated.

Therefore, sensitive, specific and non-invasive methods for a comprehensive structural and functional characterisation of living pancreatic beta cells in vivo are urgently required. This would significantly enhance our understanding of the pathophysiology of both type 1 and type 2 diabetes.

The key objective of the EU-funded 'Use of innovative strategies for beta-cell imaging in diabetes mellitus' (Betaimage) project is to develop new approaches for in vitro and in vivo beta cell imaging with a focus on beta cell mass. Given that beta cells contribute only marginally to the total mass of the pancreas and are scattered in tiny clusters known as the islets of Langerhans, a highly sensitive method for clinical imaging is required.

To this end, the consortium plans to use the imaging technology of positron emission tomography / single-photon emission computed tomography (PET / SPECT) for visualisation of beta cells in humans with a novel tracer.

So far, several potential beta cell-specific targets have been identified and specific ligands are under development. Successful in vivo determination of the pancreatic beta cell mass with a lead compound has been achieved and the acquisition and reconstruction protocols have been optimised in rodent models.

Innovative strategies including the construction of differentially labelled molecules targeting novel surface beta cell antigens are also being explored and could increase the number of potential PET applications in beta cell imaging.

The Betaimage approach for live imaging of pancreatic beta cells could be utilised not only to advance our understanding of the pathophysiology of diabetes but also to assess novel therapeutic approaches including cell replacement therapies. It is envisaged to become a great asset for diabetes research, aiding the development of novel anti-diabetic agents.