Comparative biodistribution of 12 111In-labelled gastrin/CCK2 receptor-targeting peptides

Peter Laverman, Lieke Joosten, Annemarie Eek, Susan Roosenburg, Petra Kolenc Peitl, Theodosia Maina, Helmut Mäcke, Luigi Aloj, Elisabeth Von Guggenber, Jane K. Sosabowski, Marion De Jong, Jean Claude Reubi, Wim J G Oyen, Otto C. Boerman

Research output: Contribution to journalArticle


Purpose Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in various tumours such as medullary thyroid carcinomas and small-cell lung cancers. Due to this high expression, CCK-2 receptors might be suitable targets for radionuclide imaging and/or radionuclide therapy. Several CCK-2 receptor-binding radiopeptides have been developed and some have been tested in patients. Here we aimed to compare the in vivo tumour targeting properties of 12 111Inlabelled 1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (DOTA)-conjugated gastrin/CCK2 receptor-binding peptides. Methods Two CCK8-based peptides and ten gastrin-based peptide analogues were tested. All peptides were conjugated with DOTA and labelled with 111In. Biodistribution studies were performed in mice with subcutaneous CCK2/ gastrin receptor-expressing tumours and with receptornegative tumours contralaterally. Biodistribution was studied by counting dissected tissues at 1 and 4 h after injection. Results Both the CCK analogues displayed relatively low tumour uptake (approximately 2.5%ID/g) as compared to minigastrin analogues. Two linear minigastrin peptides (MG0 and sargastrin) displayed moderate tumour uptake at both 1 and 4 h after injection, but also very high kidney uptake (both higher than 48%ID/g). The linear MG11, lacking the penta-Glu sequence, showed lower tumour uptake and also low kidney uptake. Varying the N-terminal Glu residues in the minigastrin analogues led to improved tumour targeting properties, with PP-F11 displaying the optimal biodistribution. Besides the monomeric linear peptides, a cyclized peptide and a divalent peptide were tested. Conclusion Based on these studies, optimal peptides for peptide receptor radionuclide targeting of CCK2/gastrin receptor-expressing tumours were the linear minigastrin analogue with six D-Glu residues (PP-F11), the divalent analogue MGD5 and the cyclic peptide cyclo-MG1. These peptides combined high tumour uptake with low kidney retention, and may therefore be good candidates for future clinical studies.

Original languageEnglish
Pages (from-to)1410-1416
Number of pages7
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Issue number8
Publication statusPublished - Aug 2011



  • Cholecystokinin
  • DOTA
  • Gastrin
  • Tumour

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Laverman, P., Joosten, L., Eek, A., Roosenburg, S., Peitl, P. K., Maina, T., Mäcke, H., Aloj, L., Von Guggenber, E., Sosabowski, J. K., De Jong, M., Reubi, J. C., Oyen, W. J. G., & Boerman, O. C. (2011). Comparative biodistribution of 12 111In-labelled gastrin/CCK2 receptor-targeting peptides. European Journal of Nuclear Medicine and Molecular Imaging, 38(8), 1410-1416.