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

• Published in: Bioorganic & medicinal chemistry letters Vol. 22; no. 14; pp. 4745 - 4749
• Main Authors: Chen, Yurong, Feng, Man, Li, Shilei, Xu, Jingli, Ning, Hongyu, He, Yong, Wang, Xiao, Ding, Rui, Qi, Chuanmin
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.07.2012; Elsevier
• Subjects: 18F-labeled; 4-Aminoquinazoline derivatives; animal models; Animals; Biological and medical sciences; blood; brain; chemistry; Female; Fluorine Radioisotopes - chemistry; image analysis; Medical sciences; Mice; Molecular Structure; muscles; Neoplasm Transplantation; Neoplasms - diagnosis; Organ Specificity; PET imaging agent; Pharmacology. Drug treatments; Positron-Emission Tomography; Quinazolines - chemistry; Quinazolines - pharmacokinetics; radiolabeling; Tumor detection; 18F-labeled; 4-Aminoquinazoline derivatives; PET imaging agent; Tumor detection; Evaluation; Fluorine Isotopes; Radiolabelling; Quinazoline derivatives; F-labeled; Malignant tumor; Scintigraphic agent; Detection; Chemical synthesis; Positron emission tomography; Cancer
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.05.069

This manuscript reports the design and synthesis of 18F-labeled 4-aminoquinazoline derivatives by two-step reaction with high radiochemical yield. Preliminary experiments were performed to evaluate the potential of these 18F-labeled 4-aminoquinazoline derivatives for application in PET tumor imaging. Three novel 18F-labeled 4-aminoquinazoline derivatives, N-(3-chloro-4-fluorophenyl)-6-(2-[18F]fluoroethoxy)-7-methoxyquinazolin-4-amine([18F]1), N-(3-ethynylphenyl)-6-(2-[18F]fluoroethoxy)-7-methoxyquinazolin-4-amine([18F]2), and N-(3-bromophenyl)-6-(2-[18F]fluoroethoxy)-7-methoxyquinazolin-4-amine([18F]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 [18F]3 was competitive among three 18F-labeled 4-aminoquinazoline derivatives in some aspects such as tumor/muscle uptake ratio reaching 7.70 at 60min post-injection, tumor/blood uptake ratio reaching 6.61 at 120min post-injection. So we compared radioactivity characteristics of [18F]3 with those of [18F]-FDG and L-[18F]-FET in the same animal model. The absolute radioactivity uptake of [18F]3 in tumor reached 3.31 at 60min p.i., which was slightly higher than [18F]-FDG (2.16) and L-[18F]-FET (2.75) at the same time phase. For [18F]3, tumor/muscle uptake ratio peaked 7.70 at 60min, which was obviously superior to those of [18F]-FDG and L-[18F]-FET at all time points. The tumor/brain uptake ratios of [18F]3 were 10.36, 17.42, 41.11 at 30min, 60min and 120min post-injection, respectively, and are much higher than those of L-[18F] FET (2.54, 2.92 and 2.95) and [18F]-FDG (0.61, 1.02 and 1.33) at the same time points. All these results indicate that [18F]3 is promising to become a potential PET tumor imaging agent.