title: Pancreatic β-cell imaging in humans: fiction or option?
abstract: Diabetes mellitus is a growing worldwide epidemic disease, currently affecting 1 in 12 adults. Treatment of disease complications typically consumes ∼10% of healthcare budgets in developed societies. Whilst immune-mediated destruction of insulin-secreting pancreatic β cells is responsible for Type 1 diabetes, both the loss and dysfunction of these cells underly the more prevalent Type 2 diabetes. The establishment of robust drug development programmes aimed at β-cell restoration is still hampered by the absence of means to measure β-cell mass prospectively in vivo, an approach which would provide new opportunities for understanding disease mechanisms and ultimately assigning personalized treatments. In the present review, we describe the progress towards this goal achieved by the Innovative Medicines Initiative in Diabetes, a collaborative public-private consortium supported by the European Commission and by dedicated resources of pharmaceutical companies. We compare several of the available imaging methods and molecular targets and provide suggestions as to the likeliest to lead to tractable approaches. Furthermore, we discuss the simultaneous development of animal models that can be used to measure subtle changes in β-cell mass, a prerequisite for validating the clinical potential of the different imaging tracers.
authors.affiliation: Biomarker Department, Clinical Imaging, Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Laurent
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Vinet
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Lamprianou
authors.affiliation: Metabolic Diseases Department, Servier Research Institute, Suresnes, France.
authors.forename: M
authors.initials: M
authors.lastname: Daval
authors.affiliation: Metabolic Diseases Department, Servier Research Institute, Suresnes, France.
authors.forename: G
authors.initials: G
authors.lastname: Filhoulaud
authors.affiliation: Metabolic Diseases Department, Servier Research Institute, Suresnes, France.
authors.forename: A
authors.initials: A
authors.lastname: Ktorza
authors.affiliation: Roche Pharma Research and Early Development, Innovation Center Basel, Basel, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Roche Pharma Research and Early Development, Innovation Center Basel, Basel, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Sewing
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany.
authors.forename: H-P
authors.initials: HP
authors.lastname: Juretschke
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Glombik
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Meda
authors.affiliation: Commissariat à l'Energie Atomique, Equipe d'Imagerie Moléculaire Expérimentale, Orsay, France.
authors.forename: R
authors.initials: R
authors.lastname: Boisgard
authors.affiliation: Commissariat à l'Energie Atomique, Equipe d'Imagerie Moléculaire Expérimentale, Orsay, France.
authors.forename: D L
authors.initials: DL
authors.lastname: Nguyen
authors.affiliation: Department of Chemistry, Imperial College London, London, UK.
authors.forename: G J
authors.initials: GJ
authors.lastname: Stasiuk
authors.affiliation: Department of Chemistry, Imperial College London, London, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Long
authors.affiliation: Department of Radiology, Geneva University Hospital, Geneva, Switzerland.
authors.forename: X
authors.initials: X
authors.lastname: Montet
authors.affiliation: IMIDIA Project Office, Graz, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Hecht
authors.affiliation: Scientific Consultant for Sanofi Deutschland GmbH, Frankfurt am Main, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Kramer
authors.affiliation: Section of Cell Biology and Functional Genomics, Department of Medicine, Imperial Centre for Translational and Experimental Medicine, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: G A
authors.initials: GA
authors.lastname: Rutter
authors.affiliation: Department of Histology and Imaging, Novo Nordisk Park, Måløv, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Hecksher-Sørensen
mesh_terms: D000328:Adult; D000818:Animals; D002448:Cell Adhesion; D003920:Diabetes Mellitus / Q000473:pathology*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D008163:Luminescent Measurements; D008345:Manganese; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D051381:Rats; D064233:Sulfonylurea Receptors / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism; D015032:Zinc
chemical_list: C429534:CLTRN protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D008562:Membrane Glycoproteins; D064233:Sulfonylurea Receptors; D050493:Vesicular Monoamine Transport Proteins; D008345:Manganese; D015032:Zinc
keywords: GLP-1 analogue; VMAT2; beta cell; islets; sulphonylureas; type 1 diabetes