Comparison and optimization of sterile filtration for enhanced production of [¹¹C]PIB

Objectives Simple membrane filtration method is suitable as terminal sterilization for radiopharmaceuticals because of their short half-life and radiation exposure. However, sterile filtration often causes a considerable loss of radioactivity, which is stuck in the filter membrane. In present study, various sterile filtration performance of [¹¹C]PIB was evaluated in order to find the optimal sterile filter on demand.

Methods [¹¹C]PIB was prepared from 2-(4’-aminophenyl)-6-hydroxybenzothiazole by [¹¹C]-methylation with methyl triflate reacting. After purification by semi-preparative HPLC, the product was followed by solid-phase extraction. Using eluted [¹¹C]PIB in 2 mL of ethanol, three different diluted [¹¹C]PIB (10% EtOH-saline, 50% EtOH-saline, and absolute EtOH) was prepared to measure radioactivity % of filtrate through various filters: Pall supor^® AEF (10% EtOH-saline, I), Millex^®-GS (10% EtOH-saline, II), Millex^®-GV (10% EtOH-saline, III), Millex^®-FG (50% EtOH-saline, IV) and Millex-LG^® (10% EtOH-saline, V and absolute EtOH solution, VI). The solution of [¹¹C]PIB was then passed through the individual filters and the radioactivity of filtrate and retained in the filter were assessed by means of a dose calibrator. The data expressed in non-decay corrected (n=3).

Results Pall supor^® AEF (I) and Millex^®-GS (II) were shown poor radioactivity % of filtrate with 0.9 ± 0.2 and 8.4 ± 3.1%, respectively. The radioactivity percentage passed by Millex-LG^® (V) was 69.6 ± 3.7%, while Millex^®-GV (III) and Millex^®-FG (IV) showed relatively high radioactivity % of filtrate (81.8 ± 1.6% and 80.2 ± 2.2%). The best values was found in Millex-LG^® (VI) application about 88.1 ± 2.8% (retained % on the filter membrane = 3.1 ± 0.1%). It was filtered with absolute EtOH solution containing [¹¹C]PIB and then saline was passed on the filter to adjust 10% EtOH-saline solution.

Conclusions Based on the results, the best condition (VI) was applied in the automatic device and well adapted with high sterile filtration rate (radioactivity % of filtrate = 88.9 ± 2.1%, n.d.c., n=3).