Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.
Bioorg Med Chem Lett. 2011 Aug 15;21(16):4736-41. doi: 10.1016/j.bmcl.2011.06.072. Epub 2011 Jun 23.
Two novel pyrazolo[1,5-a]pyrimidine derivatives, 7-(2-[(18)F]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ([(18)F]FEMPPC, [(18)F]1) and N-(2-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)-2-[(18)F]fluoro-4-nitrobenzamide ([(18)F]FCMPPN, [(18)F]2), have been designed and successively labeled with (18)F by the nucleophilic substitution employing tosylate and nitryl as leaving groups, respectively. The radiochemical synthesis of both compounds was completed within 60min with final high-performance liquid chromatography purification included. The corresponding radiochemical yields (without decay correction) were approximately 35% and 30%, respectively. Meanwhile, we compared the uptake characteristics of [(18)F]1 and [(18)F]2 with those of [(18)F]FDG and L-[(18)F]FET in S180 tumor cells. Furthermore, the tumor uptake of [(18)F]1 and [(18)F]2 was assessed in mice bearing S180 tumor and compared with [(18)F]FDG and L-[(18)F]FET in the same animal model. In vitro cell uptake studies showed [(18)F]1 had higher uptake than [(18)F]FDG, [(18)F]2 and L-[(18)F]FET over the 2h period. In ex vivo biodistribution showed tumor/brain uptake ratios of [(18)F]2 were 12.35, 10.44, 8.69 and 5.13 at 15 min, 30 min, 60 min and 120 min post-injection, much higher than those of L-[(18)F]FET (2.43, 2.54, 2.93 and 2.95) and [(18)F]FDG (0.59, 0.61, 1.02 and 1.33) at the same time point. What's more, the uptake of [(18)F]1 in tumor was 1.88, 4.37, 5.51, 2.95 and 2.88 at 5 min, 15 min, 30 min, 60 min and 120 min post-injection, respectively. There was a remarkable increasing trend before 30 min. The same trend was present for L-[(18)F]FET before 30 min and [(18)F]FDG before 60 min. Additionally, the tumor/brain uptake ratios of [(18)F]1 were superior to those of [(18)F]FDG at all the selected time points, the tumor/muscle and tumor/blood uptake ratios of [(18)F]1 at 30 min were higher than those of L-[(18)F]FET at the same time point. MicroPET image of [(18)F]1 administered into S180 tumor-bearing mouse acquired at 30 min post-injection illustrated that the uptake in S180 tumor was obvious. These results suggest that compound [(18)F]1 could be a new probe for PET tumor imaging.
两种新型吡唑并[1,5-a]嘧啶衍生物，7-(2-[(18)F]氟乙基氨基)-5-甲基吡唑并[1,5-a]嘧啶-3-甲腈([(18)F]FEMPPC，[(18)F]1)和 N-(2-(3-氰基-5-甲基吡唑并[1,5-a]嘧啶-7-基氨基)乙基)-2-[(18)F]氟-4-硝基苯甲酰胺([(18)F]FCMPPN，[(18)F]2)，分别通过亲核取代反应，使用 tosylate 和 nitryl 作为离去基团进行了标记。两种化合物的放射性化学合成都在 60min 内完成，最终包括高效液相色谱纯化。未经衰变校正的相应放射性化学产率约为 35%和 30%。同时，我们比较了[(18)F]1和[(18)F]2与[(18)F]FDG 和 L-[(18)F]FET 在 S180 肿瘤细胞中的摄取特性。此外，在携带 S180 肿瘤的小鼠中评估了[(18)F]1和[(18)F]2的肿瘤摄取，并与同一动物模型中的[(18)F]FDG 和 L-[(18)F]FET 进行了比较。体外细胞摄取研究表明，[(18)F]1在 2h 期间的摄取高于[(18)F]FDG、[(18)F]2和 L-[(18)F]FET。在离体生物分布研究中，[(18)F]2在注射后 15min、30min、60min 和 120min 的肿瘤/脑摄取比值分别为 12.35、10.44、8.69 和 5.13，远高于 L-[(18)F]FET(2.43、2.54、2.93 和 2.95)和[(18)F]FDG(0.59、0.61、1.02 和 1.33)在同一时间点。更重要的是，[(18)F]1在肿瘤中的摄取在注射后 5min、15min、30min、60min 和 120min 时分别为 1.88、4.37、5.51、2.95 和 2.88，在 30min 之前有明显的增加趋势。L-[(18)F]FET 在 30min 之前和[(18)F]FDG 在 60min 之前也存在相同的趋势。此外，[(18)F]1的肿瘤/脑摄取比值在所有选定的时间点均优于[(18)F]FDG，[(18)F]1在 30min 时的肿瘤/肌肉和肿瘤/血液摄取比值高于同一时间点的 L-[(18)F]FET。[(18)F]1注射到携带 S180 肿瘤的小鼠后 30min 获得的 microPET 图像表明，S180 肿瘤的摄取明显。这些结果表明，化合物[(18)F]1可能是一种用于 PET 肿瘤成像的新型探针。
