Comparative biodistribution of 12 ¹¹¹In-labelled gastrin/CCK2 receptor-targeting peptides.
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Authors
Laverman, Peter
Joosten, Lieke
Eek, Annemarie
Roosenburg, Susan
Peitl, Petra Kolenc
Maina, Theodosia
Mäcke, Helmut
von Guggenberg, Elisabeth
Sosabowski, Jane K
de Jong, Marion
Reubi, Jean-Claude
Oyen, Wim JG
Boerman, Otto C
Publication Date
2011-08Journal Title
Eur J Nucl Med Mol Imaging
ISSN
1619-7070
Publisher
Springer Science and Business Media LLC
Volume
38
Issue
8
Pages
1410-1416
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Laverman, P., Joosten, L., Eek, A., Roosenburg, S., Peitl, P. K., Maina, T., Mäcke, H., et al. (2011). Comparative biodistribution of 12 ¹¹¹In-labelled gastrin/CCK2 receptor-targeting peptides.. Eur J Nucl Med Mol Imaging, 38 (8), 1410-1416. https://doi.org/10.1007/s00259-011-1806-0
Abstract
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 (111)In-labelled 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 (111)In. Biodistribution studies were performed in mice with subcutaneous CCK2/gastrin receptor-expressing tumours and with receptor-negative 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.
Keywords
Cell Line, Tumor, Animals, Humans, Mice, Indium Radioisotopes, Peptides, Receptor, Cholecystokinin B, Inhibitory Concentration 50, Amino Acid Sequence, Protein Binding, Molecular Sequence Data, Female, Molecular Imaging
Identifiers
External DOI: https://doi.org/10.1007/s00259-011-1806-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/287415
Rights
Attribution-NonCommercial 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc/4.0/
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