One-step preparation of [18F]FPBM for PET imaging of serotonin transporter (SERT) in the brain

• Published in: Nuclear medicine and biology Vol. 43; no. 8; pp. 470 - 477
• Main Authors: Qiao, Hongwen, Zhang, Yan, Wu, Zehui, Zhu, Lin, Choi, Seok Rye, Ploessl, Karl, Kung, Hank F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2016
• Subjects: 18F; Aniline Compounds - chemical synthesis; Aniline Compounds - chemistry; Animals; Brain; Brain - diagnostic imaging; Brain - metabolism; Fluorine Radioisotopes; Macaca fascicularis; PET imaging agent; Positron-Emission Tomography - methods; Radiochemistry; Radiolabeling method; Radiology; Serotonin Plasma Membrane Transport Proteins - metabolism; Serotonin transporter; Brain; K222; SPECT; SSRI; ADAM; SERT; DASB; Serotonin transporter; FPBM; PET imaging agent; Radiolabeling method; 4-FADAM; PET; (+)-McN5652; 18F; 2-((2-((dimethylamino)methyl)-phenyl)thio)-5-iodo-phenylamine; single photon emission computed tomography; N, N-dimethyl-2-(2-amino-4-fluorophenylthio)benzyl amine; K 222; selective serotonin reuptake inhibitor; serotonin transporter; N, N-dimethyl-2-(2-amino-4-cyanophenylthio)benzyl-amine; 2-(2′-((dimethylamino)methyl)-4′-(3-fluoropropoxy)phenyl-thio)benzenamine; trans-1,2,3,5,6,10- < beta > − hexahydro-6-[4-(methylthio)phenyl-[pyrrolo-[2,1- < alpha >]isoquinoline; positron emission tomography; Kryptofix 222; F
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2016.04.003

Serotonin transporters (SERT) in the brain play an important role in normal brain function. Selective serotonin reuptake inhibitors such as fluoxetine, sertraline, paroxetine, escitalopram, etc., specifically target SERT binding in the brain. Development of SERT imaging agents may be useful for studying the function of SERT by in vivo imaging. A one-step preparation of [18F]FPBM, 2-(2′-(dimethylamino)methyl)-4′-(3-([18F]fluoropropoxy)phenylthio)benzenamine, for positron emission tomography (PET) imaging of SERT binding in the brain was achieved. An active OTs intermediate, 9, was reacted with [18F]F−/K222 to produce [18F]FPBM in one step and in high radiochemical yield. This labeling reaction was evaluated and optimized under different temperatures, bases, solvents, and varying amounts of precursor 9. The radiolabeling reaction led to the desired [18F]FPBM in one step and the crude product was purified by HPLC purification to give no-carrier-added [18F]FPBM (radiochemical yield, 24–33%, decay corrected; radiochemical purity >99%). PET imaging studies in normal monkeys (n=4) showed fast, pronounced uptakes in the midbrain and thalamus, regions known to be rich in SERT binding sites. A displacement experiment with escitalopram (5mg/kg iv injection at 30min after [18F]FPBM injection) showed a rapid and complete reversal of SERT binding, suggesting that binding by [18F]FPBM was highly specific and reversible. A one-step radiolabeling method coupled with HPLC purification for preparation of [18F]FPBM was developed. Imaging studies suggest that it is feasible to use this method to prepare [18F]FPBM for in vivo PET imaging of SERT binding in the brain.