Synthesis and evaluation of novel F-18 labeled 4-aminoquinazoline derivatives: Potential PET imaging agents for tumor detection

Three novel F-18-labeled 4-aminoquinazoline derivatives, N-(3-chloro-4-fluorophenyl)-6-(2-[F-18] fluoroethoxy)-7-methoxyquinazolin-4-amine([F-18]1), N-(3-ethynylphenyl)-6-(2-[F-18] fluoroethoxy)-7-methoxyquinazolin-4-amine([F-18]2), and N-(3-bromophenyl)-6-(2-[(18F)]fluoroethoxy)-7-methoxyquinazolin- 4-amine([F-18]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 [F-18]3 was competitive among three F-18-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 [F-18]3 with those of [F-18]-FDG and L-[F-18]-FET in the same animal model. The absolute radioactivity uptake of [F-18]3 in tumor reached 3.31 at 60 min p.i., which was slightly higher than [F-18]-FDG ( 2.16) and L-[F-18]-FET (2.75) at the same time phase. For [F-18]3, tumor/muscle uptake ratio peaked 7.70 at 60 min, which was obviously superior to those of [F-18]-FDG and L-[F-18]-FET at all time points. The tumor/brain uptake ratios of [F-18]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-[F-18] FET (2.54, 2.92 and 2.95) and [F-18]-FDG (0.61, 1.02 and 1.33) at the same time points. All these results indicate that [F-18]3 is promising to become a potential PET tumor imaging agent. (C) 2012 Elsevier Ltd. All rights reserved.