Breast tumor xenografts: diffusion-weighted MR imaging to assess early therapy with novel apoptosis-inducing anti-DR5 antibody.

Radiology
Hyunki KimKurt R Zinn

Abstract

To measure the early therapeutic response to a novel apoptosis-inducing antibody, TRA-8, by using diffusion-weighted magnetic resonance (MR) imaging in a mouse breast cancer model. Animal experiments had institutional animal care and use committee approval. Four groups of nude mice bearing luciferase-positive breast tumors (four to five mice with eight to 10 tumors per group) were injected intravenously with 0 mg (group 1), 0.025 mg (group 2), 0.100 mg (group 3), or 0.200 mg (group 4) of TRA-8 on days 0 and 3. Diffusion-weighted imaging, anatomic MR imaging, and bioluminescence imaging were performed on days 0, 3, and 6 before dosing. Averaged apparent diffusion coefficients (ADCs) for both whole tumor volume and a 1-mm peripheral tumor shell were calculated and were compared with tumor volume and living tumor cell changes. After imaging at day 6, proliferating and apoptotic cell densities were measured with Ki67 and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling, or TUNEL, staining, respectively, and were compared with cleaved caspase-3 density. The ADC increase at day 3 was dependent on TRA-8 dose level, averaging 6% +/- 3 (standard error of mean), 19% +/- 4, 14% +/- 4, and 34% +/- 7 in the whole tumor ...Continue Reading

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Citations

Jan 23, 2009·Pharmaceutical Research·Bahar ZarabiHamidreza Ghandehari
Apr 13, 2010·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Hyunki KimKurt R Zinn
Jul 7, 2011·Anti-cancer Drugs·Hyunki KimEben L Rosenthal
Jul 19, 2011·Journal of Computer Assisted Tomography·Kentaro KobayashiHiroki Shirato
Dec 29, 2011·Molecular Cancer Therapeutics·Hyunki KimKurt R Zinn
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Jun 28, 2011·AJR. American Journal of Roentgenology·Ying-Shi SunXiao-Peng Zhang
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Jul 10, 2013·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Hyunki KimKurt R Zinn
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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis