Abstract
893
Objectives: To develop an improved SERT radiotracer that can be easily labeled with F-18 for use in positron emission tomography (PET), we have prepared and evaluated a series of four biphenylthiol derivatives possessing a 4’-fluoroalkoxy group of increasing chain length.
Methods: Binding affinities were determined using LLC-PK1 cells stably overexpressing the monoamine transporters: SERT, NET, or DAT. In vivo localization of F-18 labeled ligand binding were evaluated by biodistribution studies in rats.
Results: We were able to radiolabel these derivatives with F-18 within 75-90 min and in good radiochemical yield (10-35%). All four compounds showed high binding affinity for SERT and successfully penetrated the blood brain barrier as evidenced by the brain uptake at 2 min. The compounds showed excellent target-to-nontarget (HY/CB) ratios at 120 min post-injection, and increased chain length of the 4’-fluoroalkoxy group decreased this ratio. Increased chain length increased the lipophilicity (logP) of the compound as expected.
Conclusions: The 4’-fluoroalkoxy group provided a simple site for F-18 labeling. The four compounds showed similar in vitro binding affinity profiles. C2, C3, and C4 displayed excellent brain uptake while C2 and C3 showed the best HY/CB ratios.
Research Support: Supported by a grant from NIH (MH-068782 to H.F.K.).
- Society of Nuclear Medicine, Inc.