Synthesis of fluorocholine derivatives in the detection and treatment of cancer

Victor Gonzalez
Duke University

Choline kinase activity is high in malignant cells, such that there is rapid phosphorylation of the choline that is transported into the cell. Extensive studies using magnetic resonance spectroscopy (MRS) and biochemical analyses have revealed elevated levels of choline, phosphocholine, and phosphoethanolamine in many types of cancer cells, suggesting that various choline analogs might be useful as probes in the detection of cancer provided that the analogs are sufficiently similar to choline to be recognized by the choline transporter and choline kinase. 18F-Fluorocholine has shown strong characteristics as an imaging agent for the localization and detection of cancers by positron emission tomography (PET). In this study, we describe the first preparations of two fluorocholine derivatives, fluoroacetylcholine and fluorophosphocholine. These compounds, as well as related derivatives, will be screened for toxicity agents against a range of cancer cell lines. Furthermore, the fluoromethylation of several potential targets is expected to be difficult, prompting investigation of new flurothemethylating agents such as fluoromethyltosylate.