Collectively, we demonstrated that MRx102 has potent antileukemic activity both in vitro and in vivo, has the potential to eliminate AML stem/progenitor cells and overcome microenvironmental
protection of leukemic see more cells, and warrants clinical investigation. Leukemia (2012) 26, 443-450; doi:10.1038/leu.2011.246; published online 9 September 2011″
“Introduction: 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 Cu-64-chelates have poor in vivo stability or harsh radiolabeling conditions.
Methods: In this study, two triazacyclononane analogs: C-NE3TA (4-carboxymethyl-7-[2-(carboxymethylamino)-3-(4-nitro-phenyl)-propy]-[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 Cu-64 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 SOD GDC-0973 clinical trial mice.
Results: C-NE3TA and N-NE3TA were labeled at >95% efficiency up to similar to 3.4 Ci/mu mol. 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 Cu-64-N-NE3TA and Cu-64-C-NE3TA were 96.1% and 90.5% intact after 48 h incubation in rat serum, respectively. This is compared to Cu-64 complexes of the control chelators, p-NH2-Bn-DOTA and p-NH2-Bn-NOTA, with 93.9% and 97.9% retention of Cu-64 in the complex, respectively.
OSI-744 ic50 In vivo evaluation of Cu-64-N-NE3TA and Cu-64-C-NE3TA demonstrates good clearance from normal tissues except for the liver, where 59% and 51% of the radioactivity is retained at 24 h compared to 1 h for Cu-64-N-NE3TA and Cu-64-C-NE3TA, respectively. This compares to 78% and 3% retention for Cu-64-p-NH2-Bn-DOTA and Cu-64-p-NH2-Bn-NOTA.
Conclusions: These studies demonstrate that While N-NE3TA and C-NE3TA appear to be superior chelators for Cu-64 than p-NH2-Bn-DOTA, they are not better than p-NH2-Bn-NOTA. Nevertheless, it may still be interesting to evaluate these chelators after conjugation to biomolecules. (C) 2012 Elsevier Inc. All rights reserved.”
“The rates of deamidation of alpha-synuclein and single Asn residues in 13 Asn-sequence mutants have been measured for 5 x 10(-5) M protein in both the absence and presence of 10(-2)M sodium dodecyl sulfate (SDS).