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• W2056791710 abstract "The development of novel bifunctional chelates for attaching copper-64 to biomolecules has been an active area of research for several years. However, many of these (64)Cu-chelates have poor in vivo stability or harsh radiolabeling conditions.In this study, two triazacyclononane analogs; C-NE3TA (4-carboxymethyl-7-[2-(carboxymethyl-amino)-3-(4-nitro-phenyl)-propyl]-[1,4,7]triazo-nan-1-yl-acetic acid) and N-NE3TA (4-carboxymethyl-7-[2-[carboxymethyl-(4-nitro-benzyl)-amino]-ethyl]-[1,4,7]triazonan-1-yl-acetic acid) were evaluated for their labeling efficiency with (64)Cu at room temperature and evaluated in vitro and in vivo. In vitro studies included complexation kinetics with Cu(II) using a spectrophotometric method and rat serum stability, while the in vivo biodistribution was evaluated using SCID mice.C-NE3TA and N-NE3TA were labeled at >95% efficiency up to ~3.4Ci/μmol. Both C-NE3TA and N-NE3TA formed complexes with Cu(II) almost immediately, with the Cu(II) complexation by C-NE3TA being faster than the formation of Cu(II)-N-NE3TA. Both (64)Cu-N-NE3TA and (64)Cu-C-NE3TA were 96.1% and 90.5% intact after 48h incubation in rat serum, respectively. This is compared to (64)Cu complexes of the control chelators, p-NH(2)-Bn-DOTA and p-NH(2)-Bn-NOTA, with 93.9% and 97.9% retention of (64)Cu in the complex, respectively. In vivo evaluation of (64)Cu-N-NE3TA and (64)Cu-C-NE3TA demonstrates good clearance from normal tissues except for the liver, where 59% and 51% of the radioactivity is retained at 24h compared to 1h for (64)Cu-N-NE3TA and (64)Cu-C-NE3TA, respectively. This compares to 78% and 3% retention for (64)Cu-p-NH(2)-Bn-DOTA and (64)Cu-p-NH(2)-Bn-NOTA.These studies demonstrate that while N-NE3TA and C-NE3TA appear to be superior chelators for (64)Cu than p-NH(2)-Bn-DOTA, they are not better than p-NH(2)-Bn-NOTA. Nevertheless, it may still be interesting to evaluate these chelators after conjugation to biomolecules." @default.
• W2056791710 created "2016-06-24" @default.
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• W2056791710 date "2012-11-01" @default.
• W2056791710 modified "2023-09-25" @default.
• W2056791710 title "Copper-64 radiolabeling and biological evaluation of bifunctional chelators for radiopharmaceutical development" @default.
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• W2056791710 doi "https://doi.org/10.1016/j.nucmedbio.2012.05.009" @default.
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