Objective To synthesize 18F-AlF-NOTA-G-TMTP1 and evaluate its potential for PET imaging on nude mice bearing high-metastatic potential hepatoma cells.Methods NOTA-G-TMTP1 was synthesized by the standard Fmoc-solid phase synthetic protocols and radiolabeled with 18F using NOTA-AlF chelation method.The nude mice models bearing low-metastatic potential HCC97L and high-metastatic potential HCCLM3 xenografts were established separately.The tumor-targeting characteristics of 18F-AlF-NOTA-G-TMTP1 were assessed by microPET/CT and biodistribution assay.Results NOTA-G-TMTP1 was labeled with 18F in one step with (25±6)％ labeling yield (n=5).The radiochemical purity of 18F-AlF-NOTA-G-TMTP1 was more than 95％ with a specific activity more than 11.1 GBq/μmol.The octanol/water partition coefficient (logP) for 18F-AlF-NOTA-G-TMTP1 was-3.166±0.022.The tumor to muscle ratios were 1.8± 0.4 and 4.7±0.2 at 35 min post injection for HCC97L and HCCLM3,respectively.The uptake of 18F-AlF-NOTA-G-TMTP1 in HCCLM3 tumor was inhibited (61.4％) by unlabeled G-TMTP1.Conclusion 18F-AlF-NOTA-G-TMTP1 has been successfully synthesized.It shows specific uptake by tumor induced by the high-metastatic potential hepatoma cells.

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.