Characterization of 111 In-labeled Glucose-Dependent Insulinotropic Polypeptide as a Radiotracer for Neuroendocrine Tumors

Sci Rep. 2018 Feb 13;8(1):2948. doi: 10.1038/s41598-018-21259-3.

Abstract

Somatostatin receptor targeting is considered the standard nuclear medicine technique for visualization of neuroendocrine tumors (NET). Since not all NETs over-express somatostatin receptors, the search for novel targets, visualizing these NETs, is ongoing. Many NETs, expressing low somatostatin receptor levels, express glucose-dependent insulinotropic polypeptide (GIP) receptors (GIPR). Here, we evaluated the performance of [Lys37(DTPA)]N-acetyl-GIP1-42, a newly synthesized GIP analogue to investigate whether NET imaging via GIPR targeting is feasible. Therefore, [Lys37(DTPA)]N-acetyl-GIP1-42 was radiolabeled with 111In with specific activity up to 1.2 TBq/µmol and both in vitro and in vivo receptor targeting properties were examined. In vitro, [Lys37(111In-DTPA)]N-acetyl-GIP1-42 showed receptor-mediated binding to BHK-GIPR positive cells, NES2Y cells and isolated islets. In vivo, both NES2Y and GIPR-transfected BHK tumors were visualized on SPECT/CT. Furthermore, co-administration of an excess unlabeled GIP1-42 lowered tracer uptake from 0.7 ± 0.2%ID/g to 0.6 ± 0.01%ID/g (p = 0.78) in NES2Y tumors and significantly lowered tracer uptake from 3.3 ± 0.8 to 0.8 ± 0.2%ID/g (p = 0.0001) in GIPR-transfected BHK tumors. In conclusion, [Lys37(111In-DTPA)]N-acetyl-GIP1-42 shows receptor-mediated binding in various models. Furthermore, both GIPR-transfected BHK tumors and NES2Y tumors were visible on SPECT/CT using this tracer. Therefore, [Lys37(111In-DTPA)]N-acetyl-GIP1-42 SPECT seems promising for visualization of somatostatin receptor negative NETs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Drug Stability
  • Female
  • Gastric Inhibitory Polypeptide / chemistry*
  • Gastric Inhibitory Polypeptide / metabolism
  • Gastric Inhibitory Polypeptide / pharmacokinetics
  • Humans
  • Indium Radioisotopes / chemistry*
  • Isotope Labeling
  • Kinetics
  • Mice
  • Neuroendocrine Tumors / diagnostic imaging*
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / pathology
  • Protein Transport
  • Radioactive Tracers
  • Single Photon Emission Computed Tomography Computed Tomography
  • Tissue Distribution

Substances

  • Indium Radioisotopes
  • Radioactive Tracers
  • Gastric Inhibitory Polypeptide
  • Indium-111