Key laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, People's Republic of China.
Bioorg Med Chem Lett. 2012 Jul 15;22(14):4745-9. doi: 10.1016/j.bmcl.2012.05.069. Epub 2012 May 24.
Three novel (18)F-labeled 4-aminoquinazoline derivatives, N-(3-chloro-4-fluorophenyl)-6-(2-[(18)F]fluoroethoxy)-7-methoxyquinazolin-4-amine([(18)F]1), N-(3-ethynylphenyl)-6-(2-[(18)F]fluoroethoxy)-7-methoxyquinazolin-4-amine([(18)F]2), and N-(3-bromophenyl)-6-(2-[(18)F]fluoroethoxy)-7-methoxyquinazolin-4-amine([(18)F]3) were synthesized and radiolabeled by two-step reaction with overall radiochemical yield of 21-24% (without decay corrected). Then we carried out their biodistribution experiments in S180 tumor-bearing mice. Results showed that they had certain concentration accumulation in tumor and fast clearance from muscle and blood. It was encouraging that [(18)F]3 was competitive among three (18)F-labeled 4-aminoquinazoline derivatives in some aspects such as tumor/muscle uptake ratio reaching 7.70 at 60 min post-injection, tumor/blood uptake ratio reaching 6.61 at 120 min post-injection. So we compared radioactivity characteristics of [(18)F]3 with those of [(18)F]-FDG and L-[(18)F]-FET in the same animal model. The absolute radioactivity uptake of [(18)F]3 in tumor reached 3.31 at 60 min p.i., which was slightly higher than [(18)F]-FDG (2.16) and L-[(18)F]-FET (2.75) at the same time phase. For [(18)F]3, tumor/muscle uptake ratio peaked 7.70 at 60 min, which was obviously superior to those of [(18)F]-FDG and L-[(18)F]-FET at all time points. The tumor/brain uptake ratios of [(18)F]3 were 10.36, 17.42, 41.11 at 30 min, 60 min and 120 min post-injection, respectively, and are much higher than those of L-[(18)F] FET (2.54, 2.92 and 2.95) and [(18)F]-FDG (0.61, 1.02 and 1.33) at the same time points. All these results indicate that [(18)F]3 is promising to become a potential PET tumor imaging agent.
三种新型（18）F 标记的 4-氨基喹唑啉衍生物，N-(3-氯-4-氟苯基）-6-（2-[(18)F] 氟乙氧基）-7-甲氧基喹唑啉-4-胺（[(18)F]1）、N-(3-乙炔基苯基）-6-（2-[(18)F] 氟乙氧基）-7-甲氧基喹唑啉-4-胺（[(18)F]2）和 N-(3-溴苯基）-6-（2-[(18)F] 氟乙氧基）-7-甲氧基喹唑啉-4-胺（[(18)F]3），通过两步反应合成并进行放射性标记，总放射化学产率为 21-24%（未经衰变校正）。然后，我们在 S180 荷瘤小鼠中进行了它们的生物分布实验。结果表明，它们在肿瘤中有一定的浓度积累，并且在肌肉和血液中快速清除。令人鼓舞的是，[(18)F]3 在某些方面具有竞争力，例如在注射后 60 分钟时肿瘤/肌肉摄取比达到 7.70，在注射后 120 分钟时肿瘤/血液摄取比达到 6.61，与其他两种（18）F 标记的 4-氨基喹唑啉衍生物相比。因此，我们在相同的动物模型中比较了 [(18)F]3 的放射性特征与 [(18)F]-FDG 和 L-[(18)F]-FET 的放射性特征。在注射后 60 分钟时，[(18)F]3 在肿瘤中的绝对放射性摄取达到 3.31，略高于同一时间点的 [(18)F]-FDG（2.16）和 L-[(18)F]-FET（2.75）。对于 [(18)F]3，肿瘤/肌肉摄取比在 60 分钟时达到峰值 7.70，这明显优于所有时间点的 [(18)F]-FDG 和 L-[(18)F]-FET。[(18)F]3 在注射后 30 分钟、60 分钟和 120 分钟时的肿瘤/脑摄取比分别为 10.36、17.42 和 41.11，明显高于 L-[(18)F]-FET（2.54、2.92 和 2.95）和 [(18)F]-FDG（0.61、1.02 和 1.33）在同一时间点。所有这些结果表明，[(18)F]3 有望成为一种有潜力的 PET 肿瘤成像剂。
