Fully automated synthesis and purification of 4‐(2′‐methoxyphenyl)‐1‐[2′‐(N‐2″‐pyridinyl)‐p‐[¹⁸F]fluorobenzamido]ethylpiperazine

Abstract

We have developed an efficient synthesis method for the rapid and high‐yield automated synthesis of 4‐(2′‐methoxyphenyl)‐1‐[2′‐(N‐2″‐pyridinyl)‐p‐[18F]fluorobenzamido]ethylpiperazine (p‐[18F]MPPF). No‐carrier‐added [18F]F− was trapped on a small QMA cartridge and eluted with 70% MeCN(aq) (0.4 mL) containing Kryptofix 222 (2.3 mg) and K2CO3 (0.7 mg). The nucleophilic [18F]fluorination was performed with 3 mg of the nitro‐precursor in DMSO (0.4 mL) at 190 °C for 20 min, followed by the preparative HPLC purification (column: COSMOSIL Cholester, Nacalai Tesque, Kyoto, Japan; mobile phase: MeCN/25 mm AcONH4/AcOH = 200/300/0.15; flow rate: 6.0 mL/min) to afford p‐[18F]MPPF (retention time = 9.5 min). p‐[18F]MPPF was obtained automatically with a radiochemical yield of 38.6 ± 5.0% (decay corrected, n = 5), a specific activity of 214.3 ± 21.1 GBq/µmol, and a radiochemical purity of >99% within a total synthesis time of about 55 min. Copyright © 2012 John Wiley & Sons, Ltd.

Ascertaining the Suitability of Aryl Sulfonyl Fluorides for [18F]Radiochemistry Applications: A Systematic Investigation using Microfluidics

“…The N -acetyl precursor 2a (R = 4-NHCOCH 3 -C 6 H 4 ) was radiolabeled to give [ 18 F] 2b in the greatest RCY at 30%, however, this yield is still much lower than the 78% RCY produced at 100 °C on the microfluidic system. These results are not surprising, as the use of excess equivalents of K 222 and K 2 CO 3 are known to reduce [ 18 F]fluoride incorporation and can lead to decomposition of the precursor. , On the contrary, short residence times and the superior mixing and heating capabilities of the microfluidics system may circumvent some of the decomposition problems often observed with conventional or automated synthesis conditions. Higher RCYs using conventional heating could be achieved by using 0.5 mg/mL of precursor, in acetonitrile at 100 °C for 2 min with a lower ratio of K 222 (1 mol equiv) and K 2 CO 3 (2 mol equiv).…”