Author/Editor		Laverman, Peter; Joosten, Lieke; Eek, Annemarie; Roosenburg, Susan; Kolenc-Peitl, Petra; Maina, Theodosia; Mäcke, Helmut; Aloj, Luigi; Guggenberg von, Elisabeth; Sosabowski, Jane K.; De Jong, Marion; Reubi, Jean Claude; Oyen, Wim J.G.; Boerman, Otto C.
Title		Comparative biodistribution of 12 111In-labelled gastrin/CCK2 receptor-targeting peptides
Type		članek
Vol. and No.		Letnik 38, št. 8
Publication year		2011
Volume		str. 1410-1416
ISSN		1619-7070 - European journal of nuclear medicine and molecular imaging
Language		eng
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 minigastrinanalogues 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		DOTA gastrin tumor holecistokinin