^(64)Cu-NOTA-NOC的制备及体内生物分布初步研究

Preparation and Preliminary Biodistribution Study of^(64)Cu-NOTA-NOC

对生长抑素八肽类似物NOTA-NOC进行^(64)Cu标记,并对^(64)Cu-NOTA-NOC的体外稳定性、脂水分配系数、正常及荷瘤小鼠体内分布进行初步研究。建立^(64)Cu-NOTA-NOC的标记及质控条件;考察^(64)Cu-NOTA-NOC的体外稳定性,测定其脂水分配系数;通过尾静脉注射^(64)Cu-NOTA-NOC至小鼠体内,进行生物分布研究。结果表明:室温条件下即可获得标记率大于95%的^(64)Cu-NOTA-NOC;^(64)Cu-NOTA-NOC在缓冲溶液及10%胎牛血清溶液中具有良好的稳定性,脂水分配系数为-1.12±0.0056;^(64)Cu-NOTA-NOC在正常昆明(KM)小鼠体内主要经肾脏代谢,血液摄取值随时间下降明显,显示其体内清除速度较快;在荷BON-1胰腺癌裸鼠体内也主要经肾脏代谢;在肿瘤中具有较高的摄取,注后2 h,肿瘤/肌肉摄取比值达10.38;荷BON-1胰腺癌裸鼠的PET/CT显像结果显示,1 h时,肿瘤对^(64)Cu-NOTA-NOC的摄取率最高,为7.7%ID/g,而给予阻断剂后,肿瘤对^(64)Cu-NOTA-NOC的摄取率显著降低,为0.94%ID/g。NOTA-NOC的^(64)Cu标记在室温条件下即可完成,^(64)Cu-NOTA-NOC在缓冲溶液及10%胎牛血清中具有较好的稳定性;其在动物体内主要经肾脏代谢,体内清除较快,在胰腺癌肿瘤组织中有较高摄取;PET/CT实验结果显示肿瘤对^(64)Cu-NOTA-NOC的摄取具有特异性。初步的研究结果表明,^(64)Cu-NOTA-NOC具有用于胰腺癌诊疗的潜质,值得开展进一步研究。

The radiolabeling of somatostatin octapeptide analogue NOTA-NOC with^(64)Cu was carried out.The preliminary study of^(64)Cu-NOTA-NOC on the in vitro stability,the lipid-water partition coefficient,and the distribution in normal and tumor-bearing mice was conducted.The labeling and quality control methods of^(64)Cu-NOTA-NOC were developed.The in vitro stability of^(64)Cu-NOTA-NOC was investigated in buffer solution and 10%fetal bovine serum solution at 37℃.The lipid-water partition coefficient of^(64)Cu-NOTA-NOC was also determined.Biodistribution studies were performed in normal KM mice and nude mice bearing BON-1 tumor and small-animal PET imaging studies were performed on nude mice bearing BON-1 tumor.The results showed that radiolabeling of NOTA-NOC with^(64)Cu was straightforward and fast(~15 min)at room temperature in high yield and>95%of radiochemical purity.^(64)Cu-NOTA-NOC showed good stability in buffer solution and 10%fetal bovine serum solution at 37℃.The value of Log P was-1.12±0.0056 which indicated^(64)Cu-NOTA-NOC was hydrophilic.Biodistribution studies in normal mice revealed high uptake of radioactivity in kidneys,suggesting that^(64)Cu-NOTA-NOC was mainly metabolized by the kidneys,and the blood uptake decreases significantly 4 h,indicating rapid blood clearance rate.^(64)Cu-NOTA-NOC was mainly metabolized by the kidney in nude mice bearing BON-1 tumor.At 1 h,2 h,4 h,tumor uptake was(3.74±1.23)%ID/g,(4.80±0.92)%ID/g and(1.31±0.27)%ID/g respectively,and tumor/muscle ratio reached to 10.38 at 2 h.The results of PET/CT imaging of nude mice bearing BON-1 tumor showed that the tumor uptake of^(64)Cu-NOTA-NOC peaked at 1 h,which was 7.7%ID/g,and after co-administration of the blocker,the tumor uptake of^(64)Cu-NOTA-NOC was significantly reduced to 0.94%ID/g.^(64)Cu-NOTA-NOC could be prepared under mild reaction conditions;and it had good stability in buffer solution and 10%fetal bovine serum.^(64)Cu-NOTA-NOC was mainly metabolized by kidneys,and cleared fast from the body in normal mice as well as in model mice.The tumor/muscle ratio could reach 10.38 at 2 h.The results of PET/CT imaging showed that the tumor uptake of^(64)Cu-NOTA-NOC was specific.These results demonstrated the potential of^(64)Cu-NOTA-NOC in the diagnosis of SSTR positive tumors,and it is worthy of further evaluation.