![]() ![]() Received: NovemAccepted: JanuPublished: January 25, 2010Ĭopyright: © 2010 Holland et al. ![]() PLoS ONE 5(1):Įditor: Kenji Hashimoto, Chiba University Center for Forensic Mental Health, Japan (2010) Measuring the Pharmacodynamic Effects of a Novel Hsp90 Inhibitor on HER2/ neu Expression in Mice Using 89Zr-DFO-Trastuzumab. By 72 h radiotracer uptake (73.64☑2.17%ID/g) and Western blot analysis demonstrated that HER2/ neu expression recovered to baseline levels.Ĭitation: Holland JP, Caldas-Lopes E, Divilov V, Longo VA, Taldone T, Zatorska D, et al. Expression levels of HER2/ neu were modulated during the first 24 and 48 h post-administration (29.75±4.43%ID/g and 41.42☓.64%ID/g, respectively). Pre-treatment with PU-H71 was followed by biodistribution studies and immunoPET of 89Zr-DFO-trastuzumab. In vivo biodistribution experiments revealed high specific BT-474 uptake after 24, 48 and 72 h (64.68☑3.06%ID/g 71.71☑0.35%ID/g and 85.18☑1.10%ID/g, respectively) with retention of activity for over 120 h. In vitro assays demonstrated >99% radiochemical purity with an immunoreactive fraction of 0.87☐.07. 89Zr-DFO-trastuzumab radiolabeling proceeded in high radiochemical yield and specific-activity 104.3☒.1 MBq/mg (2.82☐.05 mCi/mg of mAb). The change in 89Zr-DFO-trastuzumab tissue uptake in response to high- and low-specific-activity formulations and co-administration of PU-H71 was evaluated by biodistribution studies, Western blot analysis and immunoPET. ImmunoPET and biodistribution experiments in female, athymic nu/ nu mice bearing sub-cutaneous BT-474 (HER2/ neu positive) and/or MDA-MB-468 (HER2/ neu negative) tumor xenografts were conducted. Trastuzumab was functionalized with desferrioxamine B (DFO) and radiolabeled with Zr-oxalate at room temperature using modified literature methods.
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