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SEVENTH FRAMEWORK PROGRAMME

WP 03 - Tracer Characterisation

1. Objectives

  1. Evaluation of beta-cell tracers in animal models of diabetes and beta-cell regeneration - validation of their use in noninvasive measurement of the beta cell mass
  2. Optical coherence tomography (xf-FDOCT) for 3D dynamic real-time in vivo imaging of tracer distribution, pancreatic islets, blood fow, and beta-cell mass - validation as technological platform for tracer characterisation in vivo

2. Description

The aim of this workpackage is to validate the in vivo potential of tracers for their use in imaging of beta-cells and measurement of beta-cell mass in the pancreas. The factors that will be taken into account for selecting the tracer are uptake in vivo, specificity for beta-cells, binding retention in the target organ, labelling efficiency etc. Animal models of type 1 and type 2 diabetes will be studied, together with experimental models of beta-cell regeneration. The latter include experimental models that have been set-up by the VUB group such as regeneration of beta-cell mass induced by partial pancreatic duct ligation, and treatment of alloxan-mice with EGF and gastrin. The tracers will also be evaluated in models of genetic beta-cell ablation and beta-cell transplantation. The beta-cell mass quantification will be compared to the standard stereological morphometry method in the same animals at the end point.
Another focus of this workpackage will be the validation of xf-FDOCT as a research tool and as a technological platform for tracer characterisation within a stream-lined methodology for highly efficient tracer development for beta-cell imaging. Imaging hardware and surgical interventions required for xf-FDOCT will be optimised. Imaging protocols for determination of in vivo tracer distribution will be developed. Tracers will be labeled with fluorochromes for simultaneous xf-FDOCT and fluorescence imaging. A protocol will be developed for Doppler measurement of blood flow and a technique to determine beta-cell mass by xf-FDOCT. For this, it will be determined how to evaluate the entire beta-cell mass by studying defined areas within the pancreas.
This workpackage will closely cooperate with WP01, WP02 and WP04.
In cooperation with WP06, specific ethical issues of BetaImage will be dealt with (animal and human ethics).

3. WP leader

WP leader is Luc Bouwens - Vrije Universiteit Brussels, Belgium

4. WP partners

Radboud University Nijmegen Medical Centre, The Netherlands
Université de Genève, Switzerland
Université Libre de Bruxelles, Belgium
University of Turku, Finland
École Polytechnique Fédérale de Lausanne, Switzerland
University Hospital Freiburg, Germany

Tracer Characterisation