Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, and Molecular Imaging Program, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1182, Building 10, Room B3B69F, Bethesda, MD 20892, USA.
Radiology. 2013 Apr;267(1):173-82. doi: 10.1148/radiol.12121021. Epub 2013 Jan 17.
To evaluate the potential of anti-human epidermal growth factor receptor (HER)1- and anti-HER2-targeted radiolabeled antibodies and magnetic resonance (MR) imaging for imaging of orthotopic malignant pleural mesothelioma (MPM) in mouse models.
Animal studies with 165 mice were performed in accordance with National Institutes of Health guidelines for the humane use of animals, and all procedures were approved by the institutional Animal Care and Use Committee. Flow cytometry studies were performed to evaluate HER1 and HER2 expression in NCI-H226 and MSTO-211H mesothelioma cells. Biodistribution and single photon emission computed tomography (SPECT)/computed tomography (CT) imaging studies were performed in mice (four or five per group, depending on tumor growth) bearing subcutaneous and orthotopic MPM tumors by using HER1- and HER2-targeted indium 111 ((111)In)- and iodine 125 ((125)I)-labeled panitumumab and trastuzumab, respectively. Longitudinal MR imaging over 5 weeks was performed in three mice bearing orthotopic tumors to monitor tumor growth and metastases. SPECT/CT/MR imaging studies were performed at the final time point in the orthotopic models (n = 3). The standard unpaired Student t test was used to compare groups.
Orthotopic tumors and pleural effusions were clearly visualized at MR imaging 3 weeks after tumor cell inoculation. At 2 days after injection, the mean (111)In-panitumumab uptake of 29.6% injected dose (ID) per gram ± 2.2 (standard error of the mean) was significantly greater than the (111)In-trastuzumab uptake of 13.6% ID/g ± 1.0 and the (125)I-panitumumab uptake of 7.4% ID/g ± 1.2 (P = .0006 and P = .0001, respectively). MR imaging fusion with SPECT/CT provided more accurate information about (111)In-panitumumab localization in the tumor, as the tumor was poorly visualized at CT alone.
This study demonstrates the utility of radiolabeled anti-HER1 antibodies in the imaging of MPM in preclinical models.
http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12121021/-/DC1.
评估抗人表皮生长因子受体 (HER)1 和抗 HER2 靶向放射性标记抗体和磁共振 (MR) 成像在原位恶性胸膜间皮瘤 (MPM) 小鼠模型中的成像潜力。
根据美国国立卫生研究院关于动物人道使用的指导方针进行了 165 只小鼠的动物研究，所有程序均获得了机构动物护理和使用委员会的批准。通过流式细胞术研究评估 NCI-H226 和 MSTO-211H 间皮瘤细胞中 HER1 和 HER2 的表达。通过使用 HER1 和 HER2 靶向铟 111((111)In)-和碘 125((125)I)-标记的 panitumumab 和 trastuzumab，分别在皮下和原位 MPM 肿瘤小鼠中进行生物分布和单光子发射计算机断层扫描 (SPECT)/计算机断层扫描 (CT) 成像研究（每组四到五只，取决于肿瘤生长情况）。通过在三只患有原位肿瘤的小鼠中进行为期 5 周的纵向 MR 成像，监测肿瘤生长和转移。在原位模型的最后时间点进行 SPECT/CT/MR 成像研究（n = 3）。使用标准的未配对学生 t 检验比较组间差异。
在肿瘤细胞接种后 3 周，MR 成像可清晰显示原位肿瘤和胸腔积液。在注射后 2 天，每克 29.6%注射剂量 (ID) 的 (111)In-panitumumab 摄取量显著大于每克 13.6% ID/g 的 (111)In-trastuzumab 摄取量和每克 7.4% ID/g 的 (125)I-panitumumab 摄取量（分别为 P =.0006 和 P =.0001）。MR 成像与 SPECT/CT 的融合提供了有关 (111)In-panitumumab 在肿瘤中定位的更准确信息，因为单独 CT 成像时肿瘤显示不佳。
本研究证明了放射性标记的抗 HER1 抗体在临床前模型中用于 MPM 成像的实用性。
http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12121021/-/DC1.
