Imaging of beta cells

The insulin producing beta cells, located in the islets of Langerhans in the pancreas, play a key role in blood glucose regulation. In diabetes this blood glucose regulation is disrupted and repeated episodes of high blood glucose levels (hyperglycemia) occur. The underlying mechanism of hyperglycemia depends on the type of diabetes. Autoimmune destruction of the beta cell in type 1 diabetes (T1D) results in insulin deficiency causing hyperglycemia. In type 2 diabetes (T2D) hyperglycemia is primarily caused by insulin resistance, usually followed by loss of beta cell function and eventually beta cell mass (BCM). The changes in beta cell mass in both types of types of diabetes are poorly understood, due to the lack of a non-invasive method to measure the BCM.

We have developed a radiotracer that specifically accumulates in the beta cells and has high potential for in vivo measurement of the BCM. This tracer, radiolabeled exendin, has been characterized extensively in various animal models for both T1D and T2D and shows great potential for non-invasive measurement of the BCM. Besides measurement of the BCM in the pancreas, radiolabeled exendin could be used for monitoring beta cell loss in transplanted islets of Langerhans, a promising method for beta cell replacement therapy in T1D.

Maximum intensity projection of a SPECT/CT image of islets transplanted in the right calf muscle of a rat (red arrow). Images were acquired 1 hour post injection of 15 MBq 111In-exendin-3. Besides the signal from the transplant, radioactivity was observed in the bladder(green arrow). Source: Journal of Nuclear Medicine and Molecular Imaging

















Furthermore, novel tracers (radiolabeled and fluorescent) for in vivo targeting of beta cells are developed and their performance is evaluated in animal models for diabetes and islet transplantation.

People

Funding

  • European Union
  • Juvenile Diabetes Research Foundation (JDRF)
  • Diabetes Fonds
  • National Institute of Health (NIH)
  • European Foundation for the study of Diabetes (EFSD)

Publications

  • W.A. Eter, D. Bos, C. Frielink, O.C. Boerman, M. Brom and M. Gotthardt. "Graft revascularization is essential for non-invasive monitoring of transplanted islets with radiolabeled exendin.", Sci Rep 2015;5:15521. Abstract DOI PMID

  • C. Berclaz, C. Pache, A. Bouwens, D. Szlag, A. Lopez, L. Joosten, S. Ekim, M. Brom, M. Gotthardt, A. Grapin-Botton and T. Lasser. "Combined Optical Coherence and Fluorescence Microscopy to assess dynamics and specificity of pancreatic beta-cell tracers", Scientific Reports 2015;5:10385. Abstract/PDF DOI PMID

  • M. Brom, L. Joosten, C. Frielink, O. Boerman and M. Gotthardt. "111In-exendin uptake in the pancreas correlates with the beta cell mass and not with the alpha cell mass", Diabetes 2015;64:1324-1328. Abstract/PDF DOI PMID

  • I. Mathijs, C. Xavier, C. Peleman, V. Caveliers, M. Brom, M. Gotthardt, P.L. Herrera, T. Lahoutte and L. Bouwens. "A Standardized Method for In Vivo Mouse Pancreas Imaging and Semiquantitative $ Cell Mass Measurement by Dual Isotope SPECT", Molecular Imaging and Biology 2015;17:58-66. Abstract/PDF DOI PMID

  • M. Gotthardt, D.L. Eizirik, M. Cnop and M. Brom. "Beta cell imaging - a key tool in optimized diabetes prevention and treatment", Trends in Endocrinology and Metabolism 2014;25:375-377. Abstract/PDF DOI PMID

  • A. Jodal, B. Lankat-Buttgereit, M. Brom, R. Schibli and M. Béhé. "A comparison of three (67/68)Ga-labelled exendin-4 derivatives for $-cell imaging on the GLP-1 receptor: the influence of the conjugation site of NODAGA as chelator", EJNMMI Res 2014;4:31. Abstract/PDF DOI PMID

  • M. Brom, W. Woliner-van der Weg, L. Joosten, C. Frielink, T. Bouckenooghe, P. Rijken, K. Andralojc, B.J. Göke, M. de Jong, D.L. Eizirik, M. Béhé, T. Lahoutte, W.J.G. Oyen, C.J. Tack, M. Janssen, O.C. Boerman and M. Gotthardt. "Non-invasive quantification of the beta cell mass by SPECT with (111)In-labelled exendin", Diabetologia 2014;57:950-959. Abstract/PDF DOI PMID

  • K. Andralojc, M. Srinivas, M. Brom, L. Joosten, I.J.M. de Vries, D.L. Eizirik, O.C. Boerman, P. Meda and M. Gotthardt. "Obstacles on the way to the clinical visualisation of beta cells: looking for the Aeneas of molecular imaging to navigate between Scylla and Charybdis", Diabetologia 2012;55:1247-1257. Abstract/PDF DOI PMID