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European Journal of Nuclear Medicine and Molecular Imaging

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01-08-2011 | Original Article

Comparison of biological stability and metabolism of CCK2 receptor targeting peptides, a collaborative project under COST BM0607

Authors: Meltem Ocak, Anna Helbok, Christine Rangger, Petra Kolenc Peitl, Berthold A. Nock, Giancarlo Morelli, Annemarie Eek, Jane K. Sosabowski, Wout A. P. Breeman, Jean Claude Reubi, Clemens Decristoforo

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 8/2011

Abstract

Purpose

Stability of radiolabelled cholecystokinin 2 (CCK2) receptor targeting peptides has been a major limitation in the use of such radiopharmaceuticals especially for targeted radionuclide therapy applications, e.g. for treatment of medullary thyroid carcinoma (MTC). The purpose of this study was to compare the in vitro stability of a series of peptides binding to the CCK2 receptor [selected as part of the COST Action on Targeted Radionuclide Therapy (BM0607)] and to identify major cleavage sites.

Methods

Twelve different 1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA)-minigastrin/CCK conjugates were provided within an European COST Action (BM0607) by different laboratories and radiolabelled with ¹⁷⁷Lu. Their in vitro stabilities were tested in fresh human serum. Radiochemical yields (RCY) and intact radioligands for half-life calculations were determined by radio-HPLC. Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) analysis of metabolites was performed to identify cleavage products using conjugates labelled with excess stable ^natLu, incubated in serum at 37°C. Urine metabolite analysis after injection in normal mice was performed by radio-HPLC analysis.

Results

Variable stability in human serum was found for the different peptides with calculated half-lives between 4.5 ± 0.1 h and 198 ± 0.1 h (n = 2). In urine of normal mice only metabolised peptide fragments were detected even at short times after injection for all peptides. MALDI-TOF MS revealed a major cleavage site of all minigastrin derivatives between Asp and Phe-NH₂ at the C-terminal end.

Conclusion

Development of CCK2 receptor ligands especially for therapeutic purposes in patients with MTC or small cell lung cancer (SCLC) is still ongoing in different laboratories. This comparative study provided valuable insight into the importance of biological stability especially in the context of other results of this comparative trial within the COST Action BM0607.

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Title: Comparison of biological stability and metabolism of CCK2 receptor targeting peptides, a collaborative project under COST BM0607
Authors: Meltem Ocak
Anna Helbok
Christine Rangger
Petra Kolenc Peitl
Berthold A. Nock
Giancarlo Morelli
Annemarie Eek
Jane K. Sosabowski
Wout A. P. Breeman
Jean Claude Reubi
Clemens Decristoforo
Publication date: 01-08-2011
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 8/2011
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-011-1818-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Comparison of biological stability and metabolism of CCK2 receptor targeting peptides, a collaborative project under COST BM0607

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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