The automatic production of 16alpha-[18F]fluoroestradiol using a conventional [18F]FDG module with a disposable cassette system.

We have developed a fully automatic method for the synthesis of 16alpha-[18F]fluoroestradiol ([18F]FES) using a disposable cassette system and conventional [18F]FDG module. [18F]FES was synthesized using a GE TracerLab MX module and a modified module control program. Following [18F]fluorination, we hydrolyzed the product three times with a mixture of 2N HCl and CH(3)CN. After HPLC purification, the decay corrected radiochemical yield of [18F]FES was 45.3+/-2.8%, which was stable to 98.2+/-0.2% at 6h after synthesis. This new automated synthesis method provides high and reproducible yields with the advantage of a disposable cassette system.

Automatic synthesis of 16 alpha-[(18)F]fluoro-17beta-estradiol using a cassette-type [(18)F]fluorodeoxyglucose synthesizer.

16 alpha-[(18)F]fluoro-17beta-estradiol ([(18)F]FES) is a radiotracer for imaging estrogen receptors by positron emission tomography. We developed a clinically applicable automatic preparation system for [(18)F]FES by modifying a cassette-type [(18)F]fluorodeoxyglucose synthesizer. Two milligrams of 3-O-methoxymethyl-16,17-O-sulfuryl-16-epiestriol in acetonitrile was heated at 105 degrees C for 10 min with dried [(18)F]fluoride. The resultant solution was evaporated and hydrolyzed with 0.2 N HCl in 90% acetonitrile/water at 95 degrees C for 10 min under pressurized condition. The neutralization was carried out with 2.8% NaHCO(3), and then the high-performance liquid chromatography (HPLC) purification was performed. The desired radioactive fraction was collected and the solvent was replaced by 10 ml of saline, and then passed through a 0.22-microm filter into a pyrogen-free vial as the final product. The HPLC purification data demonstrated that [(18)F]FES was synthesized with a yield of 76.4+/-1.9% (n=5). The yield as the final product for clinical use was 42.4+/-3.2% (n=5, decay corrected). The total preparation time was 88.2+/-6.4 min, including the HPLC purification and the solvent replacement process. The radiochemical purity of the final product was >99%, and the specific activity was more than 111 GBq/micromol. The final product was stable for more than 6 h in saline containing sodium ascorbate. This new preparation system enables us to produce [(18)F]FES safe for clinical use with high and reproducible yield.

Fully automated synthesis of [18F]fluoromisonidazole using a conventional [18F]FDG module.

We developed a new fully automated method for the synthesis of [18F]fluoromisonidazole ([18F]FMISO) by modifying a commercial FDG synthesizer and its disposable fluid pathway. A three-step procedure was used to prepare the tosylate precursor, 1-(2'-nitro-1'-imidazolyl)-2-O-tetrahydrofuranyl-3-O-toluenesulfonylpropanediol. Using glycerol as the starting material, the precursor was synthesized with a yield of 21%. The optimal labeling conditions for the automated synthesis of [18F]FMISO was 10 mg of precursor in acetonitrile (2 ml heated at 105 degrees C for 360 s, followed by heating at 75 degrees C for 280 s and hydrolysis with 1 N HCl at 105 degrees C for 300 s. Using 3.7 GBq of [18F]F- as a starting activity, [18F]FMISO was obtained with high end-of-synthesis (EOS) radiochemical yields of 58.5+/-3.5% for 60.0+/-5.2 min with high-performance liquid chromatography (HPLC) purification. When solid-phase purification steps were added, the EOS radiochemical yields were 54.5+/-2.8% (337+/-25 GBq/micromol) for 70.0+/-3.8 min (n=10 for each group, decay-corrected). With a high starting radioactivity of 37.0 GBq, we obtained radiochemical yields of 54.4+/-2.9% and 52.8+/-4.2%, respectively (n=3). The solid-phase purification removed unreacted [18F]fluoride and polar impurities before the HPLC procedure. Long-term tests showed a good stability of 98.2+/-1.5%. This new automated synthesis procedure combines high and reproducible yields with the advantage of using a disposable cassette system.

Fully automated synthesis system of 3'-deoxy-3'-[18F]fluorothymidine.

We developed a new fully automated method for the synthesis of 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT), by modifying a commercial FDG synthesizer and its disposable fluid pathway. Optimal labeling condition was that 40 mg of precursor in acetonitrile (2 mL) was heated at 150 degrees C for 100 sec, followed by heating at 85 degrees C for 450 sec and hydrolysis with 1 N HCl at 105 degrees C for 300 sec. Using 3.7 GBq of [18F]F- as starting activity, [18F]FLT was obtained with a yield of 50.5 +/- 5.2% (n = 28, decay corrected) within 60.0 +/- 5.4 min including HPLC purification. With 37.0 GBq, we obtained 48.7 +/- 5.6% (n = 10). The [18F]FLT showed the good stability for 6 h. This new automated synthesis procedure combines high and reproducible yields with the benefits of a disposable cassette system.