Preclinical microPET imaging in tumor-bearing nude mice and pharmacokinetic studies of 18F-Alfatide Ⅱ
Deliang Zhang, Yesen Li, Zuoquan Zhao, Jie Lu, Yue Wang, Qian Yu, Zijing Li, Pu Zhang, Ruiqin Chen, Hua Wu, Wei Fang, Xianzhong Zhang, Xiaoyuan Chen
Abstract
ObjectiveTo assess the imaging characteristics of 18F-Alfatide Ⅱ in different tumor-bearing mice and pharmacokinetics in Beagle dogs.
MethodsBALB/c nude mice (n=24) were used for subcutaneous tumor models (A549 and U87MG), orthotopic lung cancer models (A549) and orthotopic breast cancer models (MDA-MB-231) (n=6 in each group). 18F-Alfatide Ⅱ and 18F-fluorodeoxyglucose (FDG) microPET/CT images were compared in the 4 types of tumor-bearing nude mice models. 18F-Alfatide Ⅱ blocking experiment, biodistribution experiment and imaging studies in tumors of different growth cycles were performed in A549 subcutaneous tumor-bearing nude mice models. Pharmacokinetic experiments were carried out in Beagle dogs (n=6) and CD-1 mice (n=9). Two-sample t test was used to analyze the data.
ResultsCompared with 18F-FDG, 18F-Alfatide Ⅱ microPET/CT images showed better imaging quality and contrast in subcutaneous A549, U87MG tumors and orthotopic A549 (tumor/heart: 4.50±1.17 vs 0.95±0.31; t=4.125, P<0.01), orthotopic MDA-MB-231 (tumor/muscle: 6.60±1.53 vs 0.92±0.43; t=3.984, P<0.01) transplantation nude mice models. 18F-Alfatide Ⅱ could specifically target A549 tumors, and the tumor uptake of 18F-Alfatide Ⅱ was reduced by about 75% after pre-injection with cyclo(Arg-Gly-Asp-D-Tyr-Lys)(c(RGDyk)). 18F-Alfatide Ⅱ was rapidly cleared from the blood of Beagle dogs (t1/2 was (57.34±11.69) min). It was cleared in the form of prototype drug and (69.24±6.82)% of cumulative dose was excreted through the urine within 4 h after administration.
Conclusions18F-Alfatide Ⅱ shows a higher target/non-target ratio than 18F-FDG in the imaging of A549, MDA-MB-231 and U87MG tumor-bearing nude mice models, which is more conducive to the diagnosis of tumor. 18F-Alfatide Ⅱ has excellent pharmacokinetic properties.
Key words:
Peptides, cyclic; Arg-Gly-Asp; Fluorine radioisotopes; Positron-emission tomography; Tomography, X-ray computed; Pharmacokinetics; Neoplasm transplantation; Mice; Dogs
Contributor Information
Deliang Zhang
Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
Yesen Li
Department of Nuclear Medicine, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China
Zuoquan Zhao
College of Chemistry, Beijing Normal University, Beijing 100875, China
Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China
Jie Lu
College of Chemistry, Beijing Normal University, Beijing 100875, China
Yue Wang
College of Chemistry, Beijing Normal University, Beijing 100875, China
Qian Yu
College of Chemistry, Beijing Normal University, Beijing 100875, China
Zijing Li
Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
Pu Zhang
Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
College of Chemistry, Beijing Normal University, Beijing 100875, China
Ruiqin Chen
College of Chemistry, Beijing Normal University, Beijing 100875, China
Hua Wu
Department of Nuclear Medicine, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China
Wei Fang
Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China
Xianzhong Zhang
Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
Xiaoyuan Chen
Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA
