6-^18F—Py—AMD3465的合成及荷瘤鼠microPET／CT显像研究

Synthesis of 6-^18F-Py-AMD3465 and the microPET/CT imaging of this agent in mice bearing A549 tumor

目的 制备6－^18F－Py－AMD3465，观察其在小鼠体内的生物分布，并进行荷瘤裸鼠的microPET/CT显像。方法 通过^18F直接标记AMD3465的季铵盐前体，经亲核、水解、中和3步反应得到6－^18F－Py－AMD3465，产物经HPLC分离纯化，测定其标记率和放化纯。取正常小鼠15只，分别经尾静脉注射6－^18F－Py－AMD3465各5.55 MBq，于注射后5、20、40、60、120 min各处死小鼠3只，取组织测质量及放射性计数，计算放射性摄取值（%ID/g）。将示踪剂注入A549荷瘤裸鼠体内，进行microPET/CT显像。采用配对t检验分析数据。结果 成功制备6－^18F－Py－AMD3465，合成时间约为60 min，标记率为（9.0±2.0）%，放化纯〉98%。正常小鼠静脉注射6－^18F－Py－AMD3465后，其放射性主要分布于肾、膀胱，说明主要经过肾排泄。荷瘤裸鼠的体内分布情况与正常小鼠类似，40 min时的肿瘤/肌肉比值为5.0，但肿瘤部位的放射性摄取值[（8.05±0.35） %ID/g]低于正常肺组织的（9.33±0.66） %ID/g（t＝5.26, P〈0.05）。MicroPET/CT显像结果显示，6－^18F－Py－AMD3465在荷瘤裸鼠体内仍然在肾、膀胱处存在高摄取，而肿瘤摄取值在45 min时达到最大（SUV 0.67）。结论 6－^18F－Py－AMD3465合成简单，制备方便。但其在肺癌中的摄取比正常肺组织低，将其直接用于肺部肿瘤的诊断价值有限。

Objective To synthesize 6-^18F-Py-AMD3465, to investigate its biodistribution in mice and to perform the microPET/CT imaging on mice bearing human lung cancer cell （A549）.Methods AMD3465 quaternary ammonium salt precursor was directly labeled with ^18F, then 6-^18F-Py-AMD3465 was synthesized through nucleophilic reaction, hydrolysis, neutralization and the product was purified using HPLC. The labeling yield and radiochemical purity were analyzed by HPLC. Fifteen Kunming mice were injected with 5.55 MBq of 6-^18F-Py-AMD3465 and sacrificed at 5, 20, 40, 60 and 120 min postinjection. The selected tissues were harvested and weighed, and the radioactivity in the tissues was measured by an automated γ-spectrometer. The %ID/g was calculated. MicroPET/CT studies were performed on A549-bearing mice after injecting 6-^18F-Py-AMD3465 through vena caudal. Paired t test was used.Results 6-^18F-Py-AMD3465 was successfully synthesized with the labeling yield of （9.0±2.0）%, the total synthesis time was about 60 min, and the radiochemical purity was more than 98%. Biodistribution studies showed that the radiouptake was higher in the kidneys and bladder of normal mice, which demonstrated that 6-^18F-Py-AMD3465 was mainly excreted through the kidneys. Biodistribution in A549-bearing mice was similar to that in normal mice. The tumor/muscle ratio at 40 min was 5.0, but the radiouptake of the tumor was still lower than that of the normal lung： （8.05±0.35） %ID/g vs （9.33±0.66） %ID/g; t=5.26, P〈0.05. MicroPET/CT imaging showed that the high-uptake location of 6-^18F-Py-AMD3465 in tumor-bearing mice was similar to the normal mice, and the tumor uptake reached the maximum level at 45 min post-injection （SUV 0.67）.Conclusions 6-^18F-Py-AMD3465 can be synthesized by a simple method. A lower uptake could be shown in the tumor compared to that in the lung and the tracer has limited diagnostic value for lung cancer.