PET显像剂^(18)F-AlF-NOTA-PRGD_2的肿瘤靶向性

Tumor targeting efficacy of a novel PET radiotracer ^(18)F-AlF-NOTA-PRGD_2 in mice

目的研究新型PET受体靶向显像剂18F-AlF-NOTA-PRGD2用于肿瘤显像的可行性。方法18F-AlF-NOTA-PRGD2采用18氟-氟化铝(18F-AlF)与NOTA-PRGD2在100℃下通过鳌合反应标记制备而得。荷脑胶质瘤U87MG裸鼠经尾静脉注射18F-AlFNOTA-PRGD2后行体内放射性生物学分布和PET/CT、microPET/CT显像研究。结果18F-AlF-NOTA-PRGD2采用一步法成功标记,反应时间15~20 min,标记产率为17%~25%。体内放射性生物学研究显示该显像剂能靶向肿瘤病灶,静脉注射后1 h和2h肿瘤摄取量分别达4.14±1.44、2.80±1.18%ID/g(t=1.910,P=0.070),肿瘤/脑比值分别达2.95±0.61、5.21±2.62(t=-1.686,P=0.167)。PET/CT和microPET/CT显像均可清楚显示该显像剂在荷瘤鼠体内的放射性分布情况,肿瘤显像清楚,体内分布良好,但microPET/CT图像质量明显优于PET/CT。结论18F-AlF-NOTA-PRGD2标记简单、易行,在荷瘤鼠体内具有优良的肿瘤靶向性,可发展成为PET肿瘤显像剂。

Objective To investigate the tumor targeting efficacy of ^18F-A1F-NOTA-PRGD2, a novel radiotracer of Arginine-glycine-aspartic acid （RGD） peptides. Methods ^18F-A1F-NOTA-PRGD2 was synthesized in one-step by conjugating NOTA-RGD2 with ^18F-A1F at 100℃. The tumor targeting efficacy and in vivo biodistribution profile of ^18F-A1F-NOTA-RGD2, following intravenous injection via the tail vein, were evaluated in a nude mouse model bearing subcutaneous U87MG glioblastoma xenograft by radioactivity biodistribution assessment, PET/CT and microPET/CT. Results NOTA-RGD2 was ^18F-fluorinated successfully in one-step with a yield of 17%-25% within 15-20 min. Radioactivity biodistribution study confirmed the tumor-targeting ability of ^18F-AIF-NOTA-PRGD2 in the tumor-bearing mice. At 1 and 2 h following injection, ^18F-A1F-NOTA-PRGD2 uptake in the tumor reached 4.14±1.44 and 2.80±1.18 % ID/g （t=1.910, P=0.070） with tumor/brain ratios of 2.95 ± 0.61 and 5.21 ± 2.62, respectively （t=-1.686, P=0.167）. Both PET/CT and microPET/CT were capable of showing the radioactivity biodistribution of ^18F-A1F-NOTA-PRGD2 in the mouse model and clearly displayed the tumor, but microPET/CT showed a much better image quality. Conclusion 18F-A1F-NOTA-PRGD2 prepared by one-step radiosynthesis can selectively target to the tumor, demonstrating its potential as a good radiotracer for tumor imaging. Key word： glioma; U87MG; positron emission tomography; radiotracer; receptor imaging; ^18F-A1F-NOTA-PRGD2