Application of Microreactor to the Preparation of C-11-Labeled Compounds via O-[11C]Methylation with [11C]CH3I: Rapid Synthesis of [11C]Raclopride.

A new radiolabeling method using a microreactor was developed for the rapid synthesis of [(11)C]raclopride. A chip bearing a Y-shaped mixing junction with a 200 µm (width)×20 µm (depth)×250 mm (length) flow channel was designed, and the efficiency of O-[11C]methylation was evaluated. Dimethyl sulfoxide solutions containing the O-desmethyl precursor or [11C]CH3I were introduced into separate injection ports by infusion syringes, and the radiochemical yields were measured under various conditions. The decay-corrected radiochemical yield of microreactor-derived [11C]raclopride reached 12% in 20 s at 25 °C, which was observed to increase with increasing temperature. In contrast, batch synthesis at 25 °C produced a yield of 5%: this indicates that this device could effectively achieve O-[11C]methylation in a shorter period of time. The microreactor technique may facilitate simple and efficient routine production of 11C-labeled compounds via O-[11C]methylation with [11C]CH3I.

Efficacy and safety of S-flurbiprofen plaster in knee osteoarthritis patients: A 2-week randomized controlled Phase III clinical trial compared to diclofenac gel.

AIM: S-flurbiprofen plaster (SFPP) is a novel topical nonsteroidal anti-inflammatory drug (NSAID) patch. This study aimed to assess the efficacy and safety of SFPP in knee osteoarthritis (OA) patients compared to diclofenac gel. METHODS: This study was a multicenter, randomized, active-controlled, open-label, non-inferiority phase III trial. There were 311 enrolled patients treated by SFPP or diclofenac gel for 2 weeks. The primary efficacy outcome was the knee pain when rising from the specially arranged chair assessed by visual analog scale (rVAS). The other efficacy outcomes were clinical symptoms, pain on walking, global assessment by both investigator and patient, and use/non-use of the rescue drugs during the treatment period. Adverse events (AEs) were evaluated as the safety outcome. RESULTS: The least-squares mean (95% CI) of ΔrVAS at the end of the study was 41.52 (39.16-43.88) mm in the SFPP group and 36.01 (33.69-38.33) mm in the diclofenac gel group, with a between-group difference of 5.51 (2.20-8.82), indicating non-inferiority. There were statistically significant differences between the groups in rVAS, clinical symptoms, pain on walking, and the global assessment by both investigator and patient. The incidence rate of AEs in the SFPP group was 5.8%, and there was no statistically significant difference from that in the diclofenac gel group (5.2%). Most of the AEs were mild, and no AE led to discontinuation. CONCLUSION: Non-inferiority of SFPP to diclofenac gel was demonstrated in the efficacy for pain on rising from a chair. SFPP was also well-tolerated in knee OA patients.

Continuous-Flow Synthesis of N-Succinimidyl 4-[18F]fluorobenzoate Using a Single Microfluidic Chip.

In the field of positron emission tomography (PET) radiochemistry, compact microreactors provide reliable and reproducible synthesis methods that reduce the use of expensive precursors for radiolabeling and make effective use of the limited space in a hot cell. To develop more compact microreactors for radiosynthesis of 18F-labeled compounds required for the multistep procedure, we attempted radiosynthesis of N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) via a three-step procedure using a microreactor. We examined individual steps for [18F]SFB using a batch reactor and microreactor and developed a new continuous-flow synthetic method with a single microfluidic chip to achieve rapid and efficient radiosynthesis of [18F]SFB. In the synthesis of [18F]SFB using this continuous-flow method, the three-step reaction was successfully completed within 6.5 min and the radiochemical yield was 64 ± 2% (n = 5). In addition, it was shown that the quality of [18F]SFB synthesized on this method was equal to that synthesized by conventional methods using a batch reactor in the radiolabeling of bovine serum albumin with [18F]SFB.