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Highly improved metabolic stability and pharmacokinetics of indium-111-DOTA-gastrin-conjugates for targeting of the gastrin receptorKolenc, Petra, 1976- ...The development of metabolically stable radiolabeled gastrin analogues with suitable pharmacokinetics is a topic of recent research activity. These imaging vectors are of interest because the ... gastrin/CCK2 receptor is highly overexpressed in different tumors such as medullary thyroid cancer, neuroendocrine tumors, and SCLC. The drawback of current targeting agents is either their metabolic instability or their high kidney uptake. We present the synthesis and in vitro and in vivo evaluation of 11 111In-labeled DOTA-conjugated peptides that differ by their spacer between the peptide and the chelate. We introduced uncharged but hydrophilic spacers such as oligoethyleneglycol, serine, and glutamine. The affinity of all radiopeptides was high with IC50 values between 0.5 and 4.8 nM. The improvement of human serum stability is 500-fold within this series of compounds. In addition the kidney uptake could be lowered distinctly and the tumor-to-kidney ratio improved almost 60-fold if compared with radiotracers having charged spacers such as glutamic acid.Source: Journal of medicinal chemistry. - ISSN 0022-2623 (Vol. 54, no. 8, 2011, str. 2602-2609)Type of material - article, component partPublish date - 2011Language - englishCOBISS.SI-ID - 2988401
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Kolenc, Petra, 1976- | 23364 |
Mansi, Rosalba | |
Tamma, MariaLuisa | |
Gmeiner, Tanja | 15706 |
Sollner Dolenc, Marija | 08519 |
Waser, Beatrice | |
Baum, Richard P. | |
Reubi, Jean Claude | |
Maecke, Helmut R. |
Source: Personal bibliographies
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