Pretargeted immuno-positron emission tomography imaging of carcinoembryonic antigen-expressing tumors with a bispecific antibody and a 68Ga- and 18F-labeled hapten peptide in mice with human tumor xenografts.
Pretargeted immuno-positron emission tomography imaging of carcinoembryonic antigen-expressing tumors with a bispecific antibody and a 68Ga- and 18F-labeled hapten peptide in mice with human tumor xenografts.
复制标题
DOI：
10.1158/1535-7163.mct-09-0862
复制
发表时间：
2010-04
影响因子：
5.7
通讯作者：
Boerman OC
中科院分区：
文献类型：
--
作者：
Schoffelen R;Sharkey RM;Goldenberg DM;Franssen G;McBride WJ;Rossi EA;Chang CH;Laverman P;Disselhorst JA;Eek A;van der Graaf WT;Oyen WJ;Boerman OC
18F-脱氧葡萄糖(18F-FDG)是肿瘤学中最常用的分子显像剂，对多种肿瘤的检测具有较高的敏感性和特异性。抗体可以提高特异性；因此，开发了用68Ga或18F放射性标记小的(FDG1.5kD)半抗原肽的程序，以比较它们与18F-∼的特异性，以使用预靶向程序检测肿瘤。将表达癌胚抗原(CEA；CEACAM5)的LS174T人结肠肿瘤、CEA阴性肿瘤或大腿肌肉炎症移植到小鼠体内。给小鼠注射双功能单抗(BsMAb)抗CEA×抗半抗原抗体，16h后静脉注射5MBq的68Ga或18F标记的半抗原肽。在1h内，组织对68Ga-IMP-288表现出高度和特异性的靶向性，在肿瘤中摄取10.7±3.6%ID/g，而在正常组织(如肿瘤/血69.9±32.3)、CEA阴性肿瘤(0.35±0.35%ID/g)和炎症肌肉(0.72±0.20%ID/g)中摄取很低。18F-FDG有效地定位于肿瘤(7.42±0.20%ID/g)、炎症肌肉(4.07±1.13%ID/g)和一些正常组织，因此，预靶向68Ga-IMP-288具有更好的特异性和敏感性。PET/CT图像增强了预靶向方法改进后的特异性。18F标记的IMP-449在肿瘤和正常组织中的分布与68Ga标记的IMP-288相似，表明两种标记的半抗原肽都可以使用。因此，对于短寿命的放射性核素，预靶向免疫PET表现得特别好，是一种比18F-FDG-PET更具特异性的高度敏感的程序。
18F-Fluorodeoxyglucose (18F-FDG) is the most common molecular imaging agent in oncology, with a high sensitivity and specificity for detecting a number of cancers. Antibodies could enhance specificity; therefore, procedures were developed for radiolabeling a small (∼1.5 kD) hapten-peptide with 68Ga or 18F to compare their specificity to 18F-FDG for detecting tumors using a pretargeting procedure. Mice were implanted with carcinoembryonic (CEA; CEACAM5)-expressing LS174T human colonic tumors, a CEA-negative tumor, or an inflammation was induced in thigh muscle. A bispecific monoclonal (bsMAb) anti-CEA × anti-hapten antibody was given to mice, and 16 h later, 5 MBq of 68Ga- or 18F-labeled hapten-peptides were administered intravenously. Within 1 h, tissues showed high and specific targeting of the 68Ga-IMP-288, with 10.7 ± 3.6% ID/g uptake in the tumor and very low uptake in normal tissues (e.g., tumor/blood 69.9 ± 32.3), in a CEA-negative tumor (0.35 ± 0.35% ID/g), and inflamed muscle (0.72 ± 0.20% ID/g). 18F-FDG localized efficiently in the tumor (7.42 ± 0.20% ID/g), but also in the inflamed muscle (4.07 ± 1.13% ID/g) and in a number of normal tissues; thus, pretargeted 68Ga-IMP-288 provided better specificity and sensitivity. PET/CT images reinforced the improved specificity of the pretargeting method. 18F-labeled IMP-449 distributed similarly in the tumor and normal tissues as the 68Ga-labeled IMP-288, indicating that either radiolabeled hapten-peptide could be used. Thus, pretargeted immunoPET performs exceptionally well with short-lived radionuclides, and is a highly sensitive procedure that is more specific than 18F-FDG-PET.