Abstract:
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 postinjection 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.