Synthesis and evaluation of novel F-18 labeled 4-aminoquinazoline derivatives: potential PET imaging agents for tumor detection.
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.
Key laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, People's Republic of China.
Yurong
Y
Chen
Man
M
Feng
Shilei
S
Li
Jingli
J
Xu
Hongyu
H
Ning
Yong
Y
He
Xiao
X
Wang
Rui
R
Ding
Chuanmin
C
Qi
D000818:Animals; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000175:diagnosis*; D009928:Organ Specificity; D049268:Positron-Emission Tomography; D011799:Quinazolines / Q000737:chemistry* / Q000493:pharmacokinetics
C573775:4-aminoquinazoline; D005462:Fluorine Radioisotopes; D011799:Quinazolines