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目的用抗人表皮生长因子受体(HER)1和抗HER2靶向地放射性标记抗体和MR成像评价小鼠模型原位恶性胸膜间皮瘤(MPM)影像的可能性。材料与方法动物实验采用165只小鼠,均按照国家卫生研究院的指南人道地使用动物,所有程序经动物保护和使用委员会授权。流式细胞仪对NCI-H226和MSTO-211H间皮瘤细胞中HER1和HER2的表达进行了评估。分别在小鼠皮下和原位MPM肿瘤使用HER1和HER2靶向性铟111(111In)和碘125(125I)标记帕尼单抗和曲妥单抗(根据肿瘤的生长情况,每组4或5只),对其生物学分布和单光子发射计算机体层摄影(SPECT)/CT进行研究。对3只负荷原位肿瘤的小鼠进行超过5周的纵向MR成像以检测肿瘤的生长和转移。在原位模型(n=3)的最后时间点进行了SPECT/CT/MR成像研究。采用标准非配对t检验进行组间比较。结果肿瘤细胞接种后3周MR成像可以清晰地显示原位肿瘤和胸腔积液。注射后第2天,平均111In-帕尼单抗的摄取为(29.6±2.2)%[注射剂量(ID)/g],显著大于111In-曲妥单抗的摄取[(13.6±1.0)%ID/g]和125I-帕尼单抗的摄取[(7.4±1.2)%ID/g](分别为P=0.0006和P=0.0001)。MR成像融合SPECT/CT提供了关于111In-帕尼单抗在肿瘤中定位的更精确信息,而仅在CT上肿瘤很难显示。结论这项研究表明在临床前期模型MPM的成像中放射性标记的抗HER1抗体具有实用性。
Objective To evaluate the possibility of in situ malignant pleural mesothelioma (MPM) images in mouse models using anti-human epidermal growth factor receptor (HER) 1 and anti-HER2 targeted radiolabeled antibodies and MR imaging. MATERIALS AND METHODS Animal experiments Using 165 mice, all animals were humanely used according to the guidelines of the National Institutes of Health and all procedures were authorized by the Animal Protection and Use Committee. Flow cytometry was used to assess HER1 and HER2 expression in NCI-H226 and MSTO-211H mesothelioma cells. Panitumumab and trastuzumab were labeled with HER1 and HER2 targeted indium 111 (111In) and iodine 125 (125I) respectively in mouse subcutaneous and in situ MPM tumors (4 or 5 Only) to study its biological distribution and single photon emission computed tomography (SPECT) / CT. Longitudinal MR imaging of 3 mice bearing in situ tumors over 5 weeks was performed to detect tumor growth and metastasis. SPECT / CT / MR imaging studies were performed at the last time point of the in situ model (n = 3). Standard unpaired t tests were used to compare groups. Results Three weeks after tumor cell inoculation, MR imaging clearly showed the tumor in situ and pleural effusion. On average, 111In-panitumumab uptake was (29.6 ± 2.2)% [injected dose (ID) / g] on Day 2 post injection, significantly greater than that of 111In-trastuzumab [(13.6 ± 1.0)% ID / g] and uptake of 125I-panitumumab [(7.4 ± 1.2)% ID / g] (P = 0.0006 and P = 0.0001, respectively). MR Imaging Fusion SPECT / CT provides more accurate information about the localization of 111In-panitumumab in tumors, whereas tumors are difficult to visualize on CT alone. Conclusions This study demonstrates the utility of radiolabeled anti-HER1 antibodies in the imaging of preclinical models of MPM.