Simplified synthesis ofN-(3-[18F]fluoropropyl)-2β-carbomethoxy-3β-(4-fluorophenyl)nortropane ([18F]β-CFT-FP) using [18F]fluoropropyl tosylate as the labelling reagent

Abstract

A synthesis method has been developed for the labelling of N‐(3‐[18F]fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐fluorophenyl)nortropane ([18F]β‐CFT‐FP), a potential radioligand for visualization of the dopamine transporters by positron emission tomography. The two‐step synthesis includes preparation of [18F]fluoropropyl tosylate and its use without purification in the fluoroalkylation of 2β‐carbomethoxy‐3β‐(4‐fluorophenyl)nortropane (nor‐β‐CFT). The final product is purified by HPLC. Optimization of the two synthesis steps resulted in a greater than 30% radiochemical yield of [18F]β‐CFT‐FP (decay corrected to end of bombardment). The synthesis time including HPLC‐purification was approximately 90 min. The radiochemical purity of the final product was higher than 99% and the specific radioactivity at the end of synthesis was typically 20 GBq/µmol. In comparison to alkylation by [18F]fluoropropyl bromide, the procedure described here results in an improved overall radiochemical yield of [18F]β‐CFT‐FP in a shorter time. Copyright © 2005 John Wiley & Sons, Ltd.

Comparison of 2β-Carbomethoxy-3β-(4-[18F]Fluorophenyl)Tropane and N-(3-[18F]Fluoropropyl)-2β-Carbomethoxy-3β-(4-Fluorophenyl)Nortropane, Tracers for Imaging Dopamine Transporter in Rat

“…1) was synthesized by nucleophilic fluorination at the Radiochemistry Laboratory of the University of Helsinki [20]. The SA of [ 18 F]β-CFT-FP was 36±22 GBq/μmol (EOS) and 13±9 GBq/μmol at the time of injection.…”

“…However, many of these tracers bind considerably to SERT and noradrenalin transporter (NET) and show unwanted properties like slow kinetics or fast metabolism. Based on the promising properties of [ 18 F]β-CFT [17], its fluoroethyl and fluoropropyl analogues, N-(2-[ 18 F]fluoroethyl)-2β-carbomethoxy-3β-(4-fluorophenyl)nortropane ([ 18 F]β-CFT-FE) [18,19] and [ 18 F]β-CFT-FP [18,20], have been synthesized. [ 18 F]β-CFT-FE showed reversible binding kinetics and adequate specificity for DAT in the monkey brain [19].…”

Tropane‐derived 11C‐labelled and 18F‐labelled DAT ligands

“…Its 4′‐fluoro‐analogue 33 was reported, albeit a surprisingly low specific activity was obtained. The authors explicitly state that the use of 3‐[ 18 F]fluoroprop‐1‐yl tosylate facilitated an improved yield . Radioactivity uptake into bone confounded the utility of 33 , although this is not relevant for DAT imaging in striatal brain regions, whereas cortical regions located close to the skull are prone to radiation spill over from the skull …”

Radiosynthesis of 3‐(3‐[18F]fluoropropoxy)‐4‐(benzyloxy)‐N‐[(1‐dimethylaminocyclopentyl)methyl]‐5‐methoxybenzamide, a potential PET radiotracer for the glycine transporter GlyT‐2

“…Stirring was continued for 1 h more, resulting in a white precipitate. The mixture was diluted with H 2 O, 12 M HCl was added until no pyridine odor was perceptible, and the resultant mixture was extracted several times with Methyl 3-(3-fluoropropoxy)-4-(benzyloxy)-5-methoxybenzoate (14). A mixture of compound 9 (560 mg, 1.9 mmol), 928 mg (4 mmol) 3-fluoropropyl p-toluenesulfonate and NaH (50 mg, 4 mmol) in 10 ml DMF was stirred at room temperature overnight.…”