Synthesis and Biological Evaluation of 3-O-(2-¹⁸F-fluoroethyl)-L-DOPA as A Potential PET Agent for Tumor Imaging

As a complementary category to ¹⁸F-2-fluoro-2-deoxy-D-glucose (¹⁸F-FDG), radiolabeled amino acids have been successfully employed for tumor imaging. To overcome the limitations of preparation of ¹⁸F-FDOPA, we had designed and synthesized a new ¹⁸F-radiolabeled amino acid tracer 3-O-(2-¹⁸F-fluoroethyl)-L-DOPA (¹⁸F-FEDOPA). Briefly, ¹⁸F-FEDOPA was prepared from a direct nucleophilic substitution with ¹⁸F using the new precusor, N-(tert-butoxycarbonyl)-3-(3-(2-(tosyloxy)ethoxy)-4-(tert-butoxycarbonyloxy))-L-DOPA methyl ester. The ¹⁸F-fluorinated intermediate was purified via semi-preparative HPLC and hydrolyzed by 4 mol/L HCl. After neutralized with 2 mol/L NaOH, ¹⁸F-FEDOPA was obtained as injectable solution. The overall radiochemical yield of ¹⁸F-FEDOPA was (33±6)% (n=10, decay corrected) within 90 minutes of radiosynthesis time, and the specific activity was 55 GBq/μmol. The radiochemical purity of ¹⁸F-FEDOPA (at room temperature) at 0, 60, 120 and 240 minutes were 99.35%, 98.58%, 97.98% and 97.49%, respectively, which indicated the high in vitro stability. Bio-distribution study in healthy ICR mice showed rapid clearance of ¹⁸F-FEDOPA from kidneys and low uptake in most tissues especially in brain and heart. The radioactivity in brain and heart at 60 minutes postinjection of ¹⁸F-FEDOPA were（1.01±0.18）%ID/g and （0.90±0.24）%ID/g, respectively. And there was no obvious uptake change in bone over the 90 minutes. microPET/CT imaging was performed on S180-H22 tumor-bearing ICR mice, which showed high accumulation of ¹⁸F-FEDOPA in tumor tissue. Furthermore, the ratios of tumor to brain and tumor to heart for ¹⁸F-FEDOPA (H22/brain: 7.73±2.10, S180/brain: 4.62±1.52, H22/heart: 4.33±1.22, S180/heart: 2.59±0.30) were higher than those of ¹⁸F-FDG (H22/brain: 2.14±0.71, S180/brain: 2.14±0.71, H22/heart: 1.89±0.25, S180/heart: 1.56±0.30) at 60 minutes post-injection. All these results indicated that ¹⁸F-FEDOPA would be a potential amino acid tracer for tumors PET imaging.