Automated synthesis of [18F]fluorocholine using a modified GE TracerLab module

Abstract

The automated radiosynthesis of [ 18 F]fluorocholine was carried out using a modified reactor design in

A fully-automated one-pot synthesis of [18F]fluoromethylcholine with reduced dimethylaminoethanol contamination via [18F]fluoromethyl tosylate

“…These low yields are an issue in our lab because it makes it difficult to make enough product to complete QC testing, and have sufficient dose remaining to complete the patient scan, as well as rendering it impossible to scan multiple patients from a single batch or distribute doses to satellite PET centers. Utilizing the same synthesis methods and CM Sep-Pak purification methods, other labs have reported this reaction to be higher yielding (>15% non-decay corrected), although residual DMAE levels were also frequently very high (>300 μg/mL) (Kryza et al, 2008), or not reported (Sperandeo et al, 2009). The low yields obtained in our lab can, we believe, be attributed to performing gas phase reactions on a synthesis module optimized for liquid phase chemistry.…”

“…This remains the most widely used method to date, having been adapted for SPE purification, allowing automated production with cassette-based synthesis modules such as the TRACERLab MX FDG (Kryza et al, 2008; Nader and Hoepping, 2005), a TRACERlab FX FDG (Sperandeo et al, 2009), and, in our laboratory, a TRACERLab FX FN (Shao et al, 2011b). However, in our hands and on our synthesis modules this method has proven problematic, plagued by low yields (≤4%) and, despite recently published purification improvements (Slaets et al, 2010), high DMAE contamination (≤1 mg/mL) (Shao et al, 2011a; Shao et al, 2011b).…”

“…showed that uptake of DMAE in a variety of tumor cell lines was significantly better (2–7 times higher) than that of the clinically utilized radiolabeled choline tracer (Mintz et al, 2008). Additionally, DMAE has been shown to have inhibitory effects on choline transport across the blood-brain barrier (Cornford et al, 1978), in alveolar type II epithelial cells (Dodia et al, 1992), fetal rat cerebral hemispheres (Yavin, 1980), as well as inhibiting uptake of [ 18 F]FCH in prostate cancer cells (Nader et al, 2011a; Slaets et al, 2010; Sperandeo et al, 2009). An additional study showed that residual DMAE levels (< 2.5 μM) that were lower than plasma choline levels (7–10 μM) were still significant enough to compete with [ 18 F]FCH for tumor uptake (Slaets et al, 2010).…”

Impact of Prolonged Reduced-Pressure Condition Prior to Precursor Labeling on the Labeling Efficiency of F-18 Fluorocholine Synthesis

“…Due to its high positron emission abundance, low positron energy, the small ion radius and its ease of production, fluorine-18 (F-18) become the most extensively used radioisotope for PET imaging technique. In addition, the half-life of fluorine-18 is relatively long enough to allow for multistep synthesis and transportation to remote hospitals without an on-site cyclotron [9][10].…”