Gastrin-releasing peptide receptor targeted PET imaging of 68Ga-DOTA-PEG4-BBN for prostate cancer
Objective To design and develop a molecular imaging probe of 68Ga-labeled bombesin(BBN)analogue,68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA)-polyethylene glycol(PEG)4-BBN,and investigate its potential to target prostate cancer with high expression of gastrin-releasing peptide receptor(GRPR)while minimizing uptake in pancreatic tissue.Methods Based on the amino acid sequence of BBN peptides,the precursor DOTA-PEG4-BBN was designed and prepared,fol-lowed by labeling with 68Ga and conducting to quality control analysis.The tumor uptake of 68Ga-DOTA-PEG4-BBN was assessed by microPET/CT imaging on tumor-bearing nude mice models with PC3 of high GRPR expression or HT29 of low GRPR expression(3 mice per group).68Ga-DOTA-PEG4-BBN micro-PET/CT imaging was also performed on 6 tumor-bearing nude mice models with PC3,among which 3 mice were treated with gastrin-releasing peptide antagonist 1 h prior to injection of the tracer(blocked group).After imaging,the ex vivo tissues of 3 PC3 tumor-bearing nude mice of the non-blocked group were exam-ined for radioactivity counting to evaluation the biodistribution of 68Ga-DOTA-PEG4-BBN,and the percent-age injected dose per gram of tissue(％ID/g)was calculated.Independent-sample t test was used for data analysis.Results The synthesis of 68Ga-DOTA-PEG4-BBN took 40 min,with the radiochemical yield of 50％-60％(no decay correction)and the radiochemical purity of over 95％.After incubation in the serum at 37 ℃ for 4 h,the radiochemical purity remained more than 95％.The microPET/CT imaging results indi-cated that the uptake in the PC3 tumor was 3.2 times higher than the uptake in the tumor after GRPR block-ade((1.34±0.24)vs(0.42±0.03)％ID/g;t=5.47,P=0.005).After the injection of 68Ga-DOTA-PEG4-BBN at 1 h and following imaging for 15 min,the PC3 tumor-bearing nude mice models of the non-blocked group showed that the pancreatic uptake((0.150±0.058)％ID/g)was significantly lower than that in kid-neys,lungs and liver((9.452±0.234),(0.720±0.041),(1.572±0.213)％ID/g)with a profound statis-tical distinction(t values:11.28-53.02,all P＜0.001).The tumor/pancreas uptake ratio could reach 16.92 in the tumor-bearing nude mice models with high GRPR expression.Conclusion A novel molecular ima-ging probe 68Ga-DOTA-PEG4-BBN demonstrates specific recognition of tumors with high GRPR expression while exhibiting low uptake in the pancreas,which shows its potential in prostate cancer molecular imaging.
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