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Complexes of gastrin with In3+, Ru3+ or Ga3+ ions are not recognised by the cholecystokinin 2 receptor

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Abstract

The peptide hormone gastrin (Gamide) binds trivalent metal ions, including indium (In), ruthenium (Ru) and gallium (Ga), with high affinity. Complexes of gastrin with chelated isotopes of In and Ga have previously been used for the location of tumours expressing the cholecystokinin 2 receptor (CCK2R). The aim of the present study was to purify the complexes of Gamide with radioactive isotopes of In, Ru or Ga and to investigate their ability to bind to the CCK2R. The radioactive Gamide complexes were purified on Sep-Pak C18 cartridges or by anion exchange HPLC. Binding to the CCK2R was assessed with a stably transfected clone of the gastric carcinoma cell line AGS. The 106Ru-Gamide complex could be eluted from the C18 cartridge; the 111In-Gamide and 68Ga-Gamide complexes bound irreversibly. All three complexes were successfully purified by anion exchange HPLC. The failure to detect binding of the 111In-Gamide, 106Ru-Gamide and 68Ga-Gamide complexes to the CCK2R suggests that formation of these complexes will not be useful for the detection of tumours expressing this receptor, but may instead provide alternative ways to block the actions of Gamide as a growth factor or a stimulant of gastric acid secretion.

Graphical abstract

The complexes between the hormone gastrin and radioactive 111In, 106Ru or 68Ga ions were purified by anion exchange HPLC using a NaCl gradient. The failure to detect binding of the complexes to the cholecystokinin 2 receptor suggests that metal ion treatment may provide novel approaches to block the biological actions of gastrin.

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Abbreviations

ACN:

Acetonitrile

CCK2R:

Cholecystokinin 2 receptor

DFO:

Desferrioxamine

Gamide:

Amidated gastrin17

Ggly:

Glycine-extended gastrin17

HEPES:

4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid

PBS:

Phosphate-buffered saline

PET:

Positron emission tomography

RPMI:

Roswell Park Memorial Institute medium

SEM:

Standard error of the mean

SPECT:

Single photon emission computed tomography

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Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia [Grant Number 1020983 to GSB].

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Correspondence to Marie Laval.

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Laval, M., Marshall, K.M., Sachinidis, J. et al. Complexes of gastrin with In3+, Ru3+ or Ga3+ ions are not recognised by the cholecystokinin 2 receptor. J Biol Inorg Chem 22, 999–1006 (2017). https://doi.org/10.1007/s00775-017-1478-8

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  • DOI: https://doi.org/10.1007/s00775-017-1478-8

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