[F]Fluoro-[1,2-H]choline

Choline is an important component of phospholipids in cell membranes. Increased metabolism in tissues will lead to an increased uptake of choline. Choline is phosphorylated by choline kinases (CHK) to phosphorylcholine within cells and, after several biosynthetic processes, is finally integrated into phospholipids (1). Because tumor cells have a high metabolic rate, choline uptake is high in order to keep up with the demands of the synthesis of phospholipids in their cellular membranes (2). Positron emission tomography (PET) with [C]choline has been reported to be useful for the detection and differential diagnosis of brain tumors, prostate cancer, lung cancer, and esophageal cancer (3). However, [C]choline has a high uptake in the liver, kidney, and spleen. An F-labeled choline analog was initially synthesized as [F]fluoroethylcholine ([F]FECh) to replace [C]choline as a PET tracer due to the short physical half-life of C (20 min) (4). Although F has a longer half-life (110 min), [F]FECh exhibited rapid accumulation in the urinary bladder, rendering it less desirable for imaging prostate cancer and pelvic lymph nodes. Therefore, [F]fluorocholine (FCH) was conceived to be a better biological analog than [F]FECh (5). PET studies with FCH showed high uptake in malignancies in patients with prostate cancer, breast carcinoma, and brain tumors (6, 7). Choline is also metabolized by choline oxidase in competition with CHK to choline betaine, which cannot be phosphorylated by CHK. There is a large isotope effect for the oxidation of choline to choline betaine with deuterium substitution of hydrogen on the ethanol portion of choline (8). Therefore, deuterated analogs of FCH would result in increased stability and greater tumor accumulation. Smith et al. (9) performed biodistribution studies of [F]fluoro-[1,2-H]choline ([F]12c) in tumor-bearing mice.