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.