实验动物准备对裸鼠移植瘤模型microPET 显像的影响

目的 探讨实验动物准备条件对18 F-FDG microPET 裸鼠移植瘤模型显像的影响,以选择最佳的实验动物准备条件.方法 36 只人表皮样癌细胞A431 裸鼠皮下移植瘤模型.随机分为6 组（6 只/组）;A 组：无禁食、室温（20 ～22）℃、无麻醉（注射18 F-FDG 后60 min 清醒状态）、尾静脉注射18 F-FDG;B 组：禁食（6 ～8）h、加温（30 ～32）℃、麻醉（吸入2%异氟烷麻醉）、尾静脉注射18 F-FDG;C 组：无禁食、加温、麻醉、尾静脉注射18 F-FDG;D组：禁食、室温、麻醉、尾静脉注射18 F-FDG;E 组：禁食、加温、无麻醉、尾静脉注射18 F-FDG;F 组：禁食、加温、麻醉、腹腔注射18 F-FDG.注射18 F-FDG 约1 h 后,行microPET 显像,测量皮下移植瘤、颈部肌肉、棕色脂肪、脑、肝脏、肾脏、心脏、哈氏腺最大每克组织摄取率（%ID/gmax ）.扫描前裸鼠均测血糖.结果 （1）B 组、C 组、F 组裸鼠的血糖水平与肿瘤摄取之间均呈直线负相关.（2）棕色脂肪：A 组摄取最高（8.03 ±1.29）,B 组摄取降低71.98%（P ＝0.000）.颈部肌肉：A 组摄取最高（16.07 ±5.20）,B 组摄取降低最多达81.84%（P ＝0.000）.各组脑、心脏、肝脏、肾脏、哈氏腺摄取差异无统计学意义.（3）A 组皮下移植瘤/组织或器官的摄取率最低.B 组移植瘤/颈部肌肉,移植瘤/肝脏,移植瘤/棕色脂肪的摄取率较A 组分别升高6.50 倍、1.29 倍、4.76 倍（P 均＜0.05）,肿瘤与组织或器官的图像对比度明显改善.（4）第1 次microPET 显像,尾静脉注射与腹腔注射皮下移植瘤摄取值差别无统计学意义（P ＝0.364）.第2 次microPET 显像,腹腔注射腹腔可见不同程度显像剂浓聚,其他正常组织、器官及皮下移植瘤的摄取均减低.腹腔注射方式,两次皮下移植瘤的摄取值差异有统计学意义（P ＝0.025）.结论实验动物准备明显影响18 F-FDG 在裸鼠正常组织的分布及皮下移植瘤的摄取.禁食、加温、麻醉及尾静脉注射方式,可以改善肿瘤对18 F-FDG 的摄取,保证图像有较好的稳定性及可重复性.

Effects of animal preparation on the microPET imaging in nude mouse tumor xenografts

Objective To investigate the effects of animal preparation on microPET imaging of tumor xenografts in nude mice and optimize the imaging protocol. Methods Thirty-six nude mice implanted with human epidermoid carcinoma A431cells were randomly divided into 6 groups. Group A： no fasting, room temperature （20℃ to 22℃） , no anesthesia （leaving the animal awake for 60 rain after the ^18F-FDG injection）, and ISF-FDG given by i. v. injection. Group B： Fasting （6 to 8 h） , warming （30℃ to 32% ） , anesthesia （inhaling 2% isoflurane anesthesia） , and ^18F-FDG given by i. v. injection. Group C： No fasting, warming, anesthesia, and ^18F-FDG given by i.v. injection. Group D： Fasting, room temperature, anesthesia, and ^18F-FDG given by i. v. injection. Group E： Fasting, warming, no anesthesia, and FDG given by i. v. injection. Group F： Fasting, warming, anesthesia, and ISF-FDG was given by i. p. injection. Serum glucose level was measured before FDG injection. % ID/gmax of the subcutaneous tumor, neck muscle, brown adipose tissue, brain, liver, kidney, myocardium, harderian gland of the groups A to F were measured after scanning. Results （ 1 ） The tumor ^18F-FDG uptake was significantly inversely correlated with glycemia in the groups B, C and F （P 〈 0. 05）. （2） The ^18F- FDG uptakes in the brown adipose and muscle tissues in the group A were 8.03 ± 1.29 and 16.07 ± 5.20, respectively. The ^18F-FDG uptakes in the brown adipose and muscle tissues in the group B were decreased by 71.98% and 81.84% , respectively, than that in the group A （P 〈 0.05）. The uptake in the cervical muscles was highest in the group A （ 16.07±5.20）, and lowest in the group B, being 81.84% lower than that of the group A （P =0. 000）. The uptakes by brain, liver, kidney, myocardium and harderian gland were not significantly different among different groups. （3） The tumor-to-organ uptake ratio was lowest in the group A. The tumor-to-muscle, tumor-to-liver and tumor-to-brown fat uptake ratios were 6. 5-fold, 1.29-fold and 4.76-fold increased, respectively, in the group B than that in the group A （P 〈 0.05 for all）. Under the experimental conditions of group B, the image contrast of tumor and organs was improved. （4） No significant differences were found for tumor JSF-FDG uptake by different routes of injection in the first scanning （ P =0. 364）. After the second scanning, the ^18F_FDG accumulation in the abdominal cavity by intraperitoneal injection led to a lower uptake of tumor and normal tissues. Significant differences were found for tumor ^18F-FDG uptake by intraperitoneal injection between the first scanning and the second scanning （P = 0. 025 ）. Conclusions Animal preparation has significant effects on the ^18F-FDG biodistribution in normal tissues and the uptake in subcutaneously transplanted tumors. Fasting, warming, anesthesia, intravenous injection can improve the imaging quality and reproducibility.