靶向前列腺癌胃泌素释放肽受体68Ga-DOTA-PEG4-BBN PET显像研究
Gastrin-releasing peptide receptor targeted PET imaging of 68Ga-DOTA-PEG4-BBN for prostate cancer
袁佳琪 1李迓曦 2刘杜娟 1任冉 2李梦璐 3冯宁翰 3倪建明1
作者信息
- 1. 南京医科大学附属无锡第二医院影像科,无锡 214002
- 2. 江南大学附属中心医院核医学科,无锡 214002
- 3. 南通大学附属无锡临床学院泌尿外科,南通 226007
- 折叠
摘要
目的 设计和开发一种68Ga标记的蛙皮素(BBN)类似物分子影像探针68Ga-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(DOTA)-聚乙二醇(PEG)4-BBN,研究其靶向胃泌素释放肽受体(GRPR)高表达前列腺癌及在胰腺组织中低摄取的能力.方法 基于BBN多肽的氨基酸序列,设计合成前体DOTA-PEG4-BBN,并在68Ga标记后进行质量控制.选取GRPR高表达的前列腺癌PC3荷瘤裸鼠模型和GRPR低表达的结直肠癌HT29荷瘤裸鼠模型各3只,通过microPET/CT显像对比观察68Ga-DOTA-PEG4-BBN的肿瘤摄取情况.选取PC3荷瘤裸鼠模型6只,其中3只模型鼠使用胃泌素释放肽阻断1 h,通过microPET/CT显像对比观察68Ga-DOTA-PEG4-BBN的肿瘤摄取情况.显像后,对未阻断组3只PC3荷瘤裸鼠模型的离体组织进行放射性计数,测定68Ga-DOTA-PEG4-BBN生物分布情况,以每克组织百分注射剂量率(％ID/g)表示.采用两独立样本t检验分析数据.结果 68Ga-DOTA-PEG4-BBN合成时间40 min,放射化学产率为50％～60％(未衰变校正),放化纯＞95％;血清37 ℃温育4 h,其放化纯仍＞95％.MicroPET/CT显像结果表明,PC3肿瘤部位的摄取是GRPR阻断后肿瘤部位的 3.2 倍[(1.34±0.24)与(0.42±0.03)％ID/g;t=5.47,P=0.005].未阻断组 PC3 荷瘤裸鼠模型生物分布显示,68Ga-DOTA-PEG4-BBN注射后1 h显像,15 min后胰腺的摄取[(0.150±0.058)％ID/g]明显低于肾脏、肺、肝脏的摄取[(9.452±0.234)、(0.720±0.041)、(1.572±0.213)％ID/g;t 值:11.28～53.02,均P＜0.001],探针对GRPR高表达荷瘤裸鼠模型的肿瘤/胰腺摄取比值可达16.92.结论 新型探针68Ga-DOTA-PEG4-BBN不仅能够特异性识别GRPR高表达肿瘤,还在胰腺组织中呈现低摄取,展现出其在前列腺癌分子影像诊断领域潜在的应用价值.
Abstract
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.
关键词
前列腺肿瘤/受体,铃蟾肽/同位素标记/镓放射性同位素/正电子发射断层显像术/小鼠,裸Key words
Prostatic neoplasms/Receptors,bombesin/Isotope labeling/Gallium radioisotopes/Positron-emission tomography/Mice,nude引用本文复制引用
基金项目
无锡市卫生健康委科研项目(Z202209)
无锡市"太湖人才计划"医疗卫生高层次人才项目(2020)()
上海市分子影像学重点实验室建设项目(18DZ2260400)
出版年
2024
NETL
NSTL
万方数据