Frampas Eric, Maurel Catherine, Thedrez Philippe, Remaud-Le Saëc Patricia, Faivre-Chauvet Alain, Barbet Jacques
Centre de recherche en cancérologie de Nantes-Angers CRCNA, Université de Nantes, INSERM UMR 892, 9 Quai Moncousu, Nantes, France.
Nucl Med Commun. 2011 Feb;32(2):147-54. doi: 10.1097/MNM.0b013e328341b268.
Radioimmunotherapy is emerging as a new tool for adjuvant therapy of colorectal cancer. The liver remains the main site for metastases, carrying a high mortality rate. Many animal models are available but none associates easy, reliable implantation and in-vivo follow-up for experimental therapeutic studies. The aims of this study were to develop a reliable hepatic metastatic colonic cancer model in mice using the intraportal route for injection, with follow-up by bioluminescence (BLI) and to evaluate the impact of tumor location on tumor antigen direct targeting using radiolabeled anti-CEA (carcinoembryonic antigen) antibodies.
Ls-174T Luc+ is a colon carcinoma cell line strongly expressing CEA, transfected with the luciferase gene for BLI. Isolated or aggregated cells (1×10(6)) were injected through the portal vein. The tumor burden was investigated using BLI to assess hepatic implantation and growth kinetics. The biodistribution of the 125I anti-CEA antibody fragment (F6) was studied in this model and was compared with subcutaneous implantation.
The tumor implantation rate was 100% using aggregated cells compared with 26.6% of isolated cells. Photons emitted by 1×10(6) cells were detected by BLI immediately after injection and allowed visual confirmation of hepatic distribution. The tumor growth was assessed over time to select homogeneous groups of animals. Radiolabeled anti-CEA antibody biodistributions showed a significantly higher uptake in hepatic than in subcutaneous tumors.
The association of hepatic tumor graft through the portal route and BLI provides a reliable animal model and permits sensitive in-vivo detection and follow-up of hepatic metastases. The hepatic model seems to more closely reproduce colon cancer metastases compared with subcutaneous metastasis. The hepatic model is of particular interest for studying radioimmunotherapy.
放射免疫疗法正成为结直肠癌辅助治疗的一种新工具。肝脏仍是转移的主要部位，死亡率很高。有许多动物模型可用，但没有一种能将易于操作、可靠的植入以及体内随访与实验性治疗研究相结合。本研究的目的是利用门静脉注射途径在小鼠中建立一种可靠的肝转移性结肠癌模型，并通过生物发光成像（BLI）进行随访，同时评估肿瘤位置对使用放射性标记的抗癌胚抗原（CEA）抗体直接靶向肿瘤抗原的影响。
Ls-174T Luc+是一种强烈表达CEA的结肠癌细胞系，转染了用于BLI的荧光素酶基因。将分离的或聚集的细胞（1×10⁶）经门静脉注射。使用BLI研究肿瘤负荷，以评估肝脏植入和生长动力学。在该模型中研究了¹²⁵I抗CEA抗体片段（F6）的生物分布，并与皮下植入进行比较。
与26.6%的分离细胞相比，使用聚集细胞时肿瘤植入率为100%。注射后立即通过BLI检测到1×10⁶个细胞发出的光子，从而直观确认了肝脏分布。随时间评估肿瘤生长，以选择动物的同质组。放射性标记的抗CEA抗体生物分布显示，肝脏肿瘤中的摄取明显高于皮下肿瘤。
通过门静脉途径进行肝肿瘤移植并结合BLI提供了一种可靠的动物模型，允许对肝转移进行灵敏的体内检测和随访。与皮下转移相比，肝模型似乎更能准确重现结肠癌转移。该肝模型对于研究放射免疫疗法特别有意义。
