一种靶向CA IX的多肽化合物标记与初步评价

Synthesis and Preliminary Evaluation of Peptide Compounds Targeting CA IX

为合成靶向碳酸酐酶IX(CA IX)的多肽探针^(68)Ga-DOTA-CA IX-P1-4-10,建立^(68)Ga-DOTA-CA IX-P1-4-10的标记及质控方法,对pH和前体多肽DOTA-CA IX-P1-4-10浓度对标记率的影响进行研究,确定^(68)Ga-DOTA-CA IX-P1-4-10的标记条件为:反应体系的pH为4.0~5.0(n=6),多肽DOTA-CAIX-P1-4-10浓度为15.0~40.0 mg/L(n=6),反应温度为100℃,反应时间10 min。产品为无色澄明液体、无可见异物,pH为5~7(n=6),放化纯度>99.0%(n=6),比活度为1.0~5.0 GBq/μmol(合成结束后)(n=6)。探针的脂水分配系数为-2.07±0.01(n=6),具有良好的亲水性。^(68)Ga-DOTA-CA IX-P1-4-10在生理盐水和胎牛血清中孵育4 h,放化纯度>95.0%,具有良好的体外稳定性。^(68)Ga-DOTA-CA IX-P1-4-10无异常毒性。初步评价结果表明,^(68)Ga-DOTA-CA IX-P1-4-10标记方法简单、放化纯度高、性质稳定、无异常毒性,具有开展进一步研究的价值。

In order to synthesize a peptide-based carbonic anhydrase IX(CA IX)imaging probe ^(68)Ga-DOTA-CA IX-P1-4-10,the labeling and quality control methods were developed.The effects of reaction pH and concentration of the peptide DOTA-CAIX-P1-4-10 on the labeling yield were studied.The reaction conditions were confirmed as:pH value 4.0 to 5.0(n=6),peptide DOTA-CAIX-P1-4-10 concentration 15.0 to 40.0 mg/L(n=6),reaction temperature 100℃,and reaction time 10 min.The product was clear,colorless liquid,with no visible particles.The pH of the product was 5 to 7(n=6),the radiochemical purity of ^(68)Ga-DOTA-CA IX-P1-4-10 was>99.0%(n=6),and the specific activity of ^(68)Ga-DOTA-CA IX-P1-4-10 was 1.0-5.0 GBq/μmol(end of synthesis)(n=6).The lipid-water partition coefficient of the probe was-2.07±0.01(n=6)which indicated ^(68)Ga-DOTA-CA IX-P1-4-10 was favorable hydrophilicity.^(68)Ga-DOTA-CA IX-P1-4-10 showed good in vitro stability in saline and fetal bovine serum at 37℃,and the radiochemical purity was>95.0%after 4 hours.White mice did not have abnormal behaviors in undue toxicity experiments.Preliminary results of the study showed that the probe ^(68)Ga-DOTA-CA IX-P1-4-10 is worthy of further study with a simple labeling method,high radiochemical purity,good in vitro stability and favorable biosecurity.