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 12111Inlabelled 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 with111In. 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.

Additional Metadata
Keywords Cholecystokinin, DOTA, Gastrin, Tumour
Persistent URL dx.doi.org/10.1007/s00259-011-1806-0, hdl.handle.net/1765/34545
Journal European Journal of Nuclear Medicine and Molecular Imaging
Laverman, P, Joosten, L, Eek, A, Roosenburg, S, Peitl, P.K, Maina, T, … 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. doi:10.1007/s00259-011-1806-0