HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

In vivo transchelation of copper-64 from TETA-octreotide to superoxide dismutase in rat liver.

Abstract
An understanding of the metabolic fate of radiometal-labeled peptides is important due to their application in the areas of diagnostic imaging and targeted radiotherapy. Radioisotopes of copper ((64)Cu, T(1/2) = 12.7 h; (67)Cu, T(1/2) = 62 h) have been labeled to monoclonal antibodies (mAbs) and peptides and have applications in the areas of PET imaging and targeted radiotherapy of cancer. Copper-64-TETA-D-Phe(1)-octreotide ([(64)Cu]TETA-OC) has been shown to bind to the somatostatin receptor, both in vitro and in vivo, and this agent inhibited the growth of somatostatin-receptor positive tumors in rats. Copper-64-TETA-OC, however, showed a retention of activity in the blood, liver, and bone marrow, suggesting possible dissociation of (64)Cu from TETA-OC in vivo. The purpose of this study was to determine if (64)Cu dissociates from [(64)Cu]TETA-OC and binds to the protein, superoxide dismutase (SOD) in rat liver. The liver metabolism of [(64)Cu]TETA-OC was examined in normal rats using a gel-electrophoresis assay specific for SOD and size-exclusion chromatography. The major metabolite in rat liver at 20 h postinjection had a molecular weight of 32 kDa as shown by size-exclusion chromatography. A gel electrophoresis assay specific for the detection of SOD [nitro-blue tetrazolium (NBT)] showed that a (64)Cu-labeled protein isolated from rat liver homogenates comigrated with SOD. Evaluating the metabolic fate of copper radiopharmaceuticals demonstrated that Cu(II) dissociates from macrocyclic chelators such as TETA and binds to proteins in high concentrations, namely SOD in rat liver.
AuthorsL A Bass, M Wang, M J Welch, C J Anderson
JournalBioconjugate chemistry (Bioconjug Chem) 2000 Jul-Aug Vol. 11 Issue 4 Pg. 527-32 ISSN: 1043-1802 [Print] United States
PMID10898574 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Chelating Agents
  • octreotide, TETA-Phe(1)-
  • Copper
  • Superoxide Dismutase
  • Octreotide
Topics
  • Animals
  • Chelating Agents (chemistry)
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Copper (chemistry)
  • Female
  • Liver (enzymology)
  • Octreotide (analogs & derivatives, chemistry)
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase (chemistry)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: