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Development of ¹⁸F-Fluoroethylcholine for Cancer Imaging with PET: Synthesis, Biochemistry, and Prostate Cancer Imaging

¹ Department of Radiology, International Medical Center of Japan, Tokyo, Japan
² Department of Urology, International Medical Center of Japan, Tokyo, Japan

The effectiveness of ¹¹C-choline PET in detecting various cancers, including prostate cancer, is well established. This study was aimed at developing an ¹⁸F-substituted choline analog, ¹⁸F-fluoroethylcholine (FECh), as a tracer of cancer detection. Methods: No-carrier-added ¹⁸F-FECh was synthesized by 2-step reactions: First, tetrabutylammonium (TBA) ¹⁸F-fluoride was reacted with 1,2-bis(tosyloxy)ethane to yield 2-¹⁸F-fluoroethyl tosylate; and second, 2-¹⁸F-fluoroethyl tosylate was reacted with N,N-dimethylethanolamine to yield ¹⁸F-FECh, which was then purified by chromatography. An automated apparatus was constructed for preparation of the ¹⁸F-FECh injection solution. In vitro experiments were performed to examine the uptake of ¹⁸F-FECh in Ehrlich ascites tumor cells, and the metabolites were analyzed by solvent extraction followed by various kinds of chromatography. Clinical studies of ¹⁸F-FECh PET were performed on patients with untreated primary prostate cancer as follows: A dynamic ¹⁸F-FECh PET study was performed on 1 patient and static PET studies were performed on 16 patients, and the data were compared with those of ¹¹C-choline PET on the same patients. Results: ¹⁸F-FECh was prepared in high yield and purity. The performance of the automated apparatus was excellent. The in vitro experiment revealed that ¹⁸F-FECh was incorporated into tumor cells by active transport, then phosphorylated (yielding phosphoryl-¹⁸F-FECh) in the cells, and finally integrated into phospholipids. The clinical PET studies showed marked uptake of ¹⁸F-FECh in prostate cancer. A dynamic PET study on 1 patient revealed that the blood level of ¹⁸F-FECh decreased rapidly (in 1 min), the prostate cancer level became almost maximal in a short period (1.5 min) and it remained constant for a long time (60 min), and the urinary radioactivity became prominent after a short time lag (5 min). Static PET studies conducted under bladder irrigation showed no difference between ¹⁸F-FECh uptake and ¹¹C-choline uptake in prostate cancer. However, ¹⁸F-FECh gave a slightly higher spatial resolution of the image, which was attributed to the shorter positron range of ¹⁸F. Conclusion: The synthesis of ¹⁸F-FECh was easy and reliable. ¹⁸F-FECh PET was very effective in detecting prostate cancer in patients. The chemical trap, consisting of active transport of ¹⁸F-FECh and formation of phosphoryl-¹⁸F-FECh, seemed to be involved in the uptake mechanism of ¹⁸F-FECh in tumors.

Key Words: ¹⁸F • choline • PET • prostate cancer

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