Single-chain antibodies for highly selective targeting of positron-emission-tomography (PET)-ligands and biomolecules to pancreatic islet cells in vivo

• Applicant: Professor Dr. Harald H. Klein, since 7/2010
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: from 2009 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 162901104

The ability to non-invasively measure pancreatic β-cell mass in vivo would lead to a better understanding of the pathogenesis of diabetes, provide an early diagnostic marker of type 1 and type 2 diabetes, and accelerate the development and evaluation of new therapies. Despite efforts of a number of investigators, no current approach allows for the non-invasive assessment of the β-cell mass in humans. This proposal outlines a new approach using nuclear imaging with recently developed singlechain antibodies (SCA`s) that are highly specific for rodent and human β-cells. One SCA has features indicating that it will be useful for in vivo islet imaging: rapid, specific and high volume cellular uptake into β-cells coupled with rapid elimination of unbound particles from circulation. In addition, its biodistribution in vivo after intravenous administration strongly predicted the β-cell mass. Our team with expertise in islet biology, nuclear imaging, and radiopharmaceutical synthesis will test the hypothesis that β-cell mass can be accurately assessed by PET-imaging using novel these SCA’s with these specific aims: 1) Define PET-imaging parameters using SCA radioligands. 2) Determine if PET-imaging using the newly developed SCA radioligands reflects β-cell mass in the setting of decreased β-cell mass and after islet transplantation. With the long-term goal to develop technology that can non-invasively asses islet mass in humans, these studies have been designed to investigate key scientific questions that cannot be addressed in humans using clinically relevant model systems.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Privatdozent Dr. Stephan Schneider, until 7/2010