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. 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.
Subject(s)
Coordination Complexes/metabolism , Gallium/metabolism , Gastrins/metabolism , Indium/metabolism , Receptor, Cholecystokinin B/metabolism , Ruthenium/metabolism , Cell Line , Coordination Complexes/chemistry , Gallium/chemistry , Gallium Radioisotopes/metabolism , Gastrins/chemistry , Humans , Indium/chemistry , Protein Binding , Ruthenium/chemistry , Ruthenium Radioisotopes/metabolismABSTRACT
Low molecular weight and high molecular weight metal ion binders present in blood plasma are shortly described. The binding of vanadium and ruthenium complexes by these components has received much attention, namely their interactions with human serum albumin and transferrin, and these studies are critically reviewed. The influence of the protein binding on the bioavailability of the prospective drugs, namely on the transport by blood plasma and uptake by cells is also discussed. It is concluded that vanadium compounds are mainly transported in blood by transferrin, but that no study has properly addressed the influence of albumin and transferrin in the vanadium uptake by cells. Ruthenium complexes bind strongly to HSA, most likely at the level of His residues, leading to the formation of stable adducts. If the kinetics of binding to this protein is fast enough, probably they are mainly transported by this serum protein. Nevertheless, at least for a few Ru(III)-complexes, hTf seems to play an active role in the uptake of ruthenium, while HSA may provide selectivity and higher activity for the compounds due to an enhanced permeability effect.
Subject(s)
Blood Proteins/metabolism , Coordination Complexes/blood , Ruthenium Compounds/blood , Vanadium Compounds/blood , Biological Transport , Clinical Trials as Topic , Coordination Complexes/chemistry , Coordination Complexes/metabolism , Coordination Complexes/therapeutic use , Humans , Molecular Weight , Protein Binding , Ruthenium/blood , Ruthenium/chemistry , Ruthenium/metabolism , Ruthenium Compounds/chemistry , Ruthenium Compounds/metabolism , Ruthenium Compounds/therapeutic use , Ruthenium Radioisotopes/blood , Ruthenium Radioisotopes/chemistry , Ruthenium Radioisotopes/metabolism , Ruthenium Radioisotopes/therapeutic use , Serum Albumin/metabolism , Spectrum Analysis , Transferrin/metabolism , Vanadium/blood , Vanadium/chemistry , Vanadium/metabolism , Vanadium Compounds/chemistry , Vanadium Compounds/metabolism , Vanadium Compounds/therapeutic useABSTRACT
The excretion rates for 137Cs and 106Ru after an internal contamination of CBA-mice were compared with that of 85Sr. The enhancing effect caused by 'low-temperature treatment' (+4 degrees C) observed in the case of radiostrontium was still more obvious for radiocesium but did not occur in animals contaminated with radioruthenium.
