(R)‐N‐Methyl‐3‐(3′‐[18F]fluoropropyl)phenoxy)‐3‐phenylpropanamine (18F‐MFP3) as a potential PET imaging agent for norepinephrine transporter

Abstract

A decline of norepinephrine transporter (NET) level is associated with several psychiatric and neurological disorders. Therefore positron emission tomography (PET) imaging agents are greatly desired to study the NET pathway. We have developed a C-fluoropropyl analog of nisoxetine: (R)-N-methyl-3-(3'-[(18)F]fluoropropyl)phenoxy)-3-phenylpropanamine ((18)F-MFP3) as a new potential PET radiotracer for NET with the advantage of the longer half-life of fluorine-18 (110 min compared with carbon-11 (20 min). Synthesis of (R)-N-methyl-3-(3'-fluoropropyl)phenoxy)-3-phenylpropanamine (MFP3) was achieved in five steps starting from (S)-N-methyl-3-ol-3-phenylpropanamine in approx. 3-5% overall yields. In vitro binding affinity of nisoxetine and MFP3 in rat brain homogenates labeled with (3)H-nisoxetine gave Ki values of 8.02 nM and 23 nM, respectively. For radiosynthesis of (18)F-MFP3, fluorine-18 was incorporated into a tosylate precursor, followed by the deprotection of the N-BOC-protected amine group with a 15% decay corrected yield in 2.5 h. Reverse-phase chromatographic purification provided (18)F-MFP3 in specific activities of >2000 Ci/mmol. Fluorine-18 labeled (18)F-MFP3 has been produced in modest radiochemical yields and in high specific activities. Evaluation of (18)F-MFP3 in animal imaging studies is in progress in order to validate this new fluorine-18 radiotracer for PET imaging of NET.