Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2014, 158(4):544-551 | DOI: 10.5507/bp.2013.064

Preclinical evaluation of gastrin derivatives labelled with 111In: Radiolabelling, affinity profile and pharmacokinetics in rats

Ludmila Melicharovaa, Alice Laznickovab, Milan Lazniceka
a Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic
b Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: peptides, cholecystokinin receptors, receptor targeting, minigastrins, indium-111, radiolabelling, preclinical evaluation

Received: January 15, 2013; Accepted: August 22, 2013; Prepublished online: September 27, 2013; Published: December 9, 2014  Show citation

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Melicharova, L., Laznickova, A., & Laznicek, M. (2014). Preclinical evaluation of gastrin derivatives labelled with 111In: Radiolabelling, affinity profile and pharmacokinetics in rats. Biomedical papers, 158(4), 544-551. doi: 10.5507/bp.2013.064
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