Radiosynthesis and validation of [¹⁸F]fluoroestradiol in a Synthra plus research platform for use in routine clinical practice

Abstract

In this practitioner protocol, the optimization of the radiochemical synthesis of [18F]fluoroestradiol (FES) on the Synthra RNplus research automated platform is described in detail and a quality control (QC) summary of three validation productions is presented. In comparison with published synthesis methods developed on other platforms, the yield was considerably improved (40%–45% ndc). The other important improvement is the reduction of the required concentration of H2SO4 avoiding the production of high concentrations of acidic vapors that can deteriorate the module. Purification was achieved by solid phase extraction, and the required adaptation of an external heating plate to the module to evaporate the ethanol is also described. The product was obtained with high radiochemical purity and fulfilled all the requirements of current Good Manufacturing Practice (cGMP). The final product is formulated as a sterile, pyrogen‐free solution suitable for human injection. To the best of our knowledge, this is the first report of FES production using this type of module.

Synthesis of a [18F]F Estradiol Derivative via Click Chemistry Using an Automated Synthesis Module: In Vitro Evaluation as Potential Radiopharmaceutical for Breast Cancer Imaging

“…The radiofluorination of B with [ 18 F]fluoride was performed on the Synthra RNplus Research automated synthesis module under conditions selected based on the literature and the previous experience of our group [ 35 , 38 ]. The reaction was performed at 90 °C for 20 min, using Kryptofix (Sigma Aldricht, San Luis, MI, USA) and K 2 CO 3 .…”

“…The radiofluorination of C with 18 F was pursued by nucleophilic substitution on a Synthra RNplus Research automated synthesis module. The procedure consists of the incubation of precursor C dissolved in DMSO, using Kryptofix ® (Sigma Aldricht, San Luis, MI, USA) as a phase transfer catalyst in combination with K 2 CO 3 to give a basic medium at 50 • C for 30 min [35,38]. The reaction was monitored by HPLC using a gamma detector.…”

“…We concluded that the low yield of the reaction was a consequence of the decomposition of the precursor compound C due to the harsh conditions required by the direct method of radiofluorination and consequently decided to switch to method 2. The radiofluorination of B with [ 18 F]fluoride was performed on the Synthra RNplus Research automated synthesis module under conditions selected based on the literature and the previous experience of our group [35,38]. The reaction was performed at 90 • C for 20 min, using Kryptofix (Sigma Aldricht, San Luis, MI, USA) and K 2 CO 3 .…”