A nanobody-based tracer targeting DPP6 for non-invasive imaging of human pancreatic endocrine cells

Sci Rep. 2017 Nov 9;7(1):15130. doi: 10.1038/s41598-017-15417-2.


There are presently no reliable ways to quantify endocrine cell mass (ECM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. To address this unmet need, we coupled RNA sequencing of human pancreatic islets to a systems biology approach to identify new biomarkers of the endocrine pancreas. Dipeptidyl-Peptidase 6 (DPP6) was identified as a target whose mRNA expression is at least 25-fold higher in human pancreatic islets as compared to surrounding tissues and is not changed by proinflammatory cytokines. At the protein level, DPP6 localizes only in beta and alpha cells within the pancreas. We next generated a high-affinity camelid single-domain antibody (nanobody) targeting human DPP6. The nanobody was radiolabelled and in vivo SPECT/CT imaging and biodistribution studies were performed in immunodeficient mice that were either transplanted with DPP6-expressing Kelly neuroblastoma cells or insulin-producing human EndoC-βH1 cells. The human DPP6-expressing cells were clearly visualized in both models. In conclusion, we have identified a novel beta and alpha cell biomarker and developed a tracer for in vivo imaging of human insulin secreting cells. This provides a useful tool to non-invasively follow up intramuscularly implanted insulin secreting cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / metabolism*
  • Humans
  • Insulin-Secreting Cells / cytology*
  • Mice
  • Nerve Tissue Proteins / metabolism*
  • Potassium Channels / metabolism*
  • Protein Transport*
  • Sequence Analysis, RNA
  • Single Photon Emission Computed Tomography Computed Tomography / methods*
  • Single-Domain Antibodies / metabolism*
  • Staining and Labeling / methods*


  • Nerve Tissue Proteins
  • Potassium Channels
  • Single-Domain Antibodies
  • DPP6 protein, human
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases