Abstract
Cholecystokinin receptor subtype 2 (CCK-2) is overexpressed in various tumours like medullary thyroid carcinomas and small cell lung cancer. Radiolabelled peptides that bind with high affinity and specificity to CCK-2 receptors, thus hold great potential for visualizing such tumours. We compared four 111In labelled gastrin analogues, called minigastrins (MG), namely MG11, MG45, MG47 and MG48 linked to metal chelating DOTA in preclinical experiments. The radiolabelled peptides were tested for peptide binding in CCK-2 receptor-bearing cell line AR42J and for their pharmacokinetics in normal rats. The experiments suggest that all gastrin analogues had similar and relatively rapid internalization into AR42J cells. Binding to CCK-2 receptors in AR42J cells was saturable for all agents but there were some differences in receptor affinity. This biodistribution study in rats showed a rapid decrease in blood radioactivity, predominantly renal clearance and saturable uptake of the radiopharmaceutical and/or its metabolites in the CCK-2 receptor-positive stomach. Higher kidney accumulation of radioactivity was only found for 111In-DOTA-minigastrin 48. The data suggest that the 111In-DOTA-minigastrin analogues studied are promising candidates for the scintigraphy of CCK-2 receptor-expressing tumours; 111In-DOTA-MG47 and 111In-DOTA-MG11 are the most promising.
Highlights
Radiolabelled receptor-specific peptides hold promise for early diagnosis or treatment of diseases
Behr et al.[7] developed DTPA-derivatized D-Glu1-minigastrin (MG0); the peptide labelled with 111In or 90Y had high uptake in stomach and tumour lesions in patients with metastatic thyroid medullary carcinomas[8]
Radiolabelling with 111In Labelling of DOTA-minigastrins was achieved by incubating the agents at 80 oC for 15 min in the presence of 111InCl3
Summary
Radiolabelled receptor-specific peptides hold promise for early diagnosis or treatment of diseases. As cholecystokinin receptor subtype 2 (CCK-2) is overexpressed in a high percentage in a large number of neuroendocrine tumours, in particular medullary thyroid carcinoma, small cell lung cancer, astrocytomas, and neuroendocrine gut tumours, CCK-2 receptor which has high affinity for gastrin, might be a suitable target for radionuclide imaging and therapy. As cholecystokinin receptor subtype 2 (CCK-2) is overexpressed in a high percentage in a large number of neuroendocrine tumours, in particular medullary thyroid carcinoma, small cell lung cancer, astrocytomas, and neuroendocrine gut tumours, CCK-2 receptor which has high affinity for gastrin, might be a suitable target for radionuclide imaging and therapy3-6 For this reason, the development of radiolabelled CCK2receptor targeting peptides has gained relevant interest in both cancer visualization and receptor-mediated therapy. The data suggest that the 111In-DOTA-minigastrin analogues studied are promising candidates for the scintigraphy of CCK-2 receptor-expressing tumours; 111In-DOTA-MG47 and 111In-DOTA-MG11 are the most promising
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