Objective To investigate the feasibility of a PET radionuclide,caspase-3-activatable probe containing Asp-Glu-Val-Asp (DEVD),for imaging evaluation of tumor apoptosis in vivo.Methods ( 18S,21 S,24S,27S,30S) -27-( 2-carboxyethyl ) -21-(carboxymethyl) -30-( ( 2S,3 R,4R,5R,6S) -6-( ( 2-(4-(3-[ 18 F ] fluoropropyl ) -1 H-1,2,3-triazol-1-yl ) acetamido ) methyl ) -3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxamido) -24-isopropyl-18 -methyl-17,20,23,26,29-pentaoxo-4,7,10,13-tetraoxa-16,19,22,25,28-pentaazadotriacontane-1,32-dioic acid (18F-FP-peptide) was automatically synthesized using a domestic synthesis module by click chemistry.In vitro cellular uptake of 18F-FP-peptide was evaluated by mixing the peptide with lung adenocarcinoma A549 cells after chemotherapy by carboplatin.Apoptosis was monitored by flow cytometry.The correlation between cellular uptake and the apoptotic ratio was analyzed.In vivo biodistribution and micro PET imaging were performed on A549 tumor bearing mice with or without chemotherapy.SPSS 13.0 was used for statistical analysis.Comparison among groups was conducted by one-way analysis of variance,and correlation was analyzed by linear correlation and regression.Results The yield of 18 F-FP-peptide was (21.0 ± 4.5)% (n =6,end of synthesis (EOS)).The radiochemistry purity was over 99% and the specific activity was 870 GBq/μmol.After the in vitro treatment of A549 cells,the apoptotic ratio was (1.02 ±0.31)%,(4.85 ±1.26)%,(6.37 ±2.21)% and (10.23 ±2.43)% at 0,1,2 and 24 h,respectively.The corresponding cellular uptake of 18F-FP-peptide was (0.06 ± 0.01 )%,(0.31 ± 0.04) %,(0.44 ± 0.02) % and (0.86 ± 0.04) %.Significant positive correlation was found between the apoptosis ratio and cellular uptake of 18F-FP-peptide (y =1.1244 + 11.0949x,r =0.9850,P <0.01).The tumor uptake of A549 beating mice at 24 h after chemotherapy was (0.33 ±0.02) % ID/g,which was significantly higher than that of the control ( (0.08 ±0.01 ) % ID/g,F =31.25,P <0.01 ).The cell apoptotic ratios were ( 15.50 ± 1.47) % for tumors undergoing chemotherapy and ( 1.92 ± 0.31 ) % for the control group (F =33.54,P < 0.01 ).Significant positive correlation was also found between the apoptotic ratio and the tumor uptake of 18 F-FP-peptide in vivo (y =- 1.9055 + 54.4341x,r =0.9907,P < 0.01 ).Micro PET images displayed that there was almost no uptake in the untreated tumor (SUV ratio =1.32 ±0.01 ) but significantly increased uptake of 18F-FP-peptide in the treated tumor ( SUV ratio =3.46 ±0.02,F =11.05,P <0.01 ).Conclusion 18 F-FP-peptide can be a potential radiotracer for caspase-3 imaging in tissue apoptosis. Key words: Peptides; Isotope labeling; Fluorine radioisotopes; Chemical synthesis; Tomography,emission-computed; Tumor cell, cultured; Apoptosis; Mice