Targeting of a CCK(2) receptor splice variant with (111)In-labelled cholecystokinin-8 (CCK8) and (111)In-labelled minigastrin

Eur J Nucl Med Mol Imaging. 2008 Feb;35(2):386-92. doi: 10.1007/s00259-007-0604-1. Epub 2007 Oct 13.


Purpose: Radiolabelled cholecystokinin (CCK) and gastrin-derived peptides potentially can be used for peptide receptor radionuclide therapy (PRRT). Recently, a splice variant version of the CCK2R has been identified, designated CCK2i4svR. Constitutive expression of this receptor has been demonstrated in human colorectal cancer and in pancreatic cancer, but not in normal tissue. So far, it has never been shown whether radiolabelled peptides can target the CCK2i4svR in vivo. In this paper, we investigated the potential of sulfated (111)In-labelled DOTA-CCK8 (sCCK8), a pan-CCKR-binding peptide, and [(111)In]DOTA-minigastrin (MG0), a CCK2R selective peptide, for the targeting of the CCK2i4svR.

Materials and methods: The receptor binding affinity of [(111)In]DOTA-sCCK8 and [(111)In]DOTA-MG0 for the CCK2R and CCK2i4svR was determined using stably transfected HEK293 cell lines, expressing either CCK2R or CCK2i4svR. Tumour targeting was studied in HEK293-CCK2i4svR tumour-bearing athymic mice.

Results: [(111)In]DOTA-sCCK8 as well as [(111)In]DOTA-MG0 specifically bound both CCK2R and CCK2i4svR with affinities in the low nanomolar range. In vivo experiments revealed that accumulation of both peptides in CCK2i4svR-positive tumours was similar (3.21 +/- 0.77 and 3.01 +/- 0.67%ID/g, sCCK8 and MG0, respectively, 24 h p.i.). Kidney retention of [(111)In]DOTA-MG0 (32.4 +/- 7.5%ID/g, 24 h p.i.) was markedly higher than that of [(111)In]DOTA-sCCK8 (2.75 +/- 0.31%ID/g, 24 h p.i.).

Conclusion: We demonstrated that the CCK2i4svR is a potential target for PRRT using a radiolabelled sulfated CCK8 peptide. As this receptor is expressed on colorectal and pancreatic tumours, but not in normal tissue, these tumours are potentially new targets for PRRT with CCK8 and gastrin analogs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cholecystokinin / metabolism*
  • Colorectal Neoplasms / diagnostic imaging
  • Colorectal Neoplasms / metabolism*
  • Drug Delivery Systems / methods*
  • Female
  • Gastrins / chemistry
  • Gastrins / pharmacokinetics*
  • Humans
  • Indium Radioisotopes / chemistry
  • Indium Radioisotopes / pharmacokinetics*
  • Isotope Labeling / methods
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Organ Specificity
  • Peptide Fragments / metabolism*
  • Protein Isoforms / metabolism*
  • Radionuclide Imaging
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics
  • Receptor, Cholecystokinin B / genetics
  • Receptor, Cholecystokinin B / metabolism*
  • Tissue Distribution


  • Gastrins
  • Indium Radioisotopes
  • Peptide Fragments
  • Protein Isoforms
  • Radiopharmaceuticals
  • Receptor, Cholecystokinin B
  • cholecystokinin 8
  • minigastrin
  • Cholecystokinin