Desilva Alan, Wuest Melinda, Wang Monica, Hummel Jeff, Mossman Karen, Wuest Frank, Hitt Mary M
Department of Oncology, University of Alberta - Cross Cancer Institute Edmonton, AB - T6G 1Z2, Canada.
Am J Nucl Med Mol Imaging. 2012;2(1):88-98. Epub 2011 Dec 15.
Positron emission tomography (PET) allows detection of functional changes in malignant tissue. Establishment of an immortalized immunocompetent breast cancer mouse model would provide a useful platform for the analysis of novel cancer treatment strategies. This study describes a comparative functional evaluation of murine breast cancer models established from polyoma virus middle T antigen (PyMT)-derived tumors using small animal PET imaging with [(18)F]FDG and [(18)F]FLT. Primary PyMT tumor-derived cells and a cell line derived from these tumors (MTHJ) were injected subcutaneously into immunocompetent FVB mice to generate breast cancer xenografts. Tumor growth rates were comparable in both models and tumors were analyzed after 4-5 weeks post-injection. [(18)F]FDG uptake in vitro followed a comparable trend in both models but reached higher uptake levels in primary PyMT cells vs. MTHJ cells after 120 min. At all time points, [(18)F]FLT uptake was significantly higher in MTHJ compared to primary PyMT cells. Dynamic small animal PET imaging with [(18)F]FDG revealed standardized uptake values (SUVs) of 2.5±0.1 (n=8) in tumors from primary cells and 2.8±0.4 (n=6) in MTHJ tumors after 60 min p.i.. The corresponding tumor-muscle-ratios were 9.3±1.5 and 10.4±0.9, respectively. Uptake of [(18)F]FLT resulted in slightly higher SUV(60min) in MTHJ tumors (1.1±0.1, n=6) compared to tumors from primary cells (SUV(60min)=0.9±0.05, n=8, p=0.07). The tumor-muscle-ratio was comparable in both tumors (2.1±0.2 and 1.8±0.1, respectively). The PET imaging data demonstrates that the functional profile of immunocompetent murine breast tumor model MTHJ remains the same as in primary-derived PyMT tumors in vivo. Metabolic and proliferative rates as assessed with [(18)F]FDG and [(18)F]FLT are comparable in both tumor models. The observed high SUV(60min) of 2.8±0.4 with [(18)F]FDG in MTHJ tumors allows one to monitor efficacy of therapeutic interventions connected with changes in metabolic response of the tumor by means of small animal PET.
正电子发射断层扫描（PET）能够检测恶性组织中的功能变化。建立永生化免疫活性乳腺癌小鼠模型将为分析新型癌症治疗策略提供一个有用的平台。本研究描述了使用小动物PET成像，采用[（18）F]FDG和[（18）F]FLT对由多瘤病毒中T抗原（PyMT）衍生的肿瘤建立的小鼠乳腺癌模型进行的比较功能评估。将原发性PyMT肿瘤衍生细胞和源自这些肿瘤的细胞系（MTHJ）皮下注射到免疫活性FVB小鼠中以生成乳腺癌异种移植物。两个模型中的肿瘤生长速率相当，在注射后4 - 5周对肿瘤进行分析。体外[（18）F]FDG摄取在两个模型中遵循相似的趋势，但在120分钟后，原发性PyMT细胞中的摄取水平高于MTHJ细胞。在所有时间点，MTHJ中[（18）F]FLT摄取均显著高于原发性PyMT细胞。用[（18）F]FDG进行的动态小动物PET成像显示，注射后60分钟，原发性细胞来源的肿瘤标准化摄取值（SUVs）为2.5±0.1（n = 8），MTHJ肿瘤为2.8±0.4（n = 6）。相应的肿瘤 - 肌肉比分别为9.3±1.5和10.4±0.9。与原发性细胞来源的肿瘤相比，MTHJ肿瘤中[（18）F]FLT摄取导致的SUV（60分钟）略高（1.1±0.1，n = 6），原发性细胞来源的肿瘤SUV（60分钟）= 0.9±0.05，n = 8，p = 0.07。两种肿瘤的肿瘤 - 肌肉比相当（分别为2.1±0.2和1.8±0.1）。PET成像数据表明，免疫活性小鼠乳腺肿瘤模型MTHJ在体内的功能特征与原发性PyMT肿瘤相同。用[（18）F]FDG和[（18）F]FLT评估的代谢和增殖率在两种肿瘤模型中相当。在MTHJ肿瘤中观察到的[（18）F]FDG的高SUV（60分钟）值为2.8±0.4，这使得能够通过小动物PET监测与肿瘤代谢反应变化相关的治疗干预的疗效。
