Preclinical microPET imaging in tumor-bearing nude mice and pharmacokinetic studies of 18F-Alfatide II
10.3760/cma.j.issn.2095-2848.2019.04.003
- VernacularTitle:18F-阿法肽荷瘤裸鼠模型显像与药代动力学研究
- Author:
Deliang ZHANG
1
;
Yesen LI
;
Zuoquan ZHAO
;
Jie LU
;
Yue WANG
;
Qian YU
;
Zijing LI
;
Pu ZHANG
;
Ruiqin CHEN
;
Hua WU
;
Wei FANG
;
Xianzhong ZHANG
;
Xiaoyuan CHEN
Author Information
1. 厦门大学分子影像暨转化医学研究中心 361102
- Keywords:
Peptides,cyclic;
Arg-Gly-Asp;
Fluorine radioisotopes;
Positron-emission tomography;
Tomography,X-ray computed;
Pharmacokinetics;
Neoplasm transplantation;
Mice;
Dogs
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2019;39(4):201-206
- CountryChina
- Language:Chinese
-
Abstract:
Objective To assess the imaging characteristics of 18F-Alfalide II in different tumorbearing mice and pharmacokinetics in Beagle dogs.Methods BALB/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.Results Compared 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.Conclusions 18F-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.
