A general method for the fluorine‐18 labelling of fluoroquinolone antibiotics

Fluoroquinolones are an important class of antibiotic agents with a broad spectrum of antibacterial activity. Labelling of fluoroquinolones with fluorine‐18 is of interest for the performance of pharmacokinetic measurements and the visualization of bacterial infections in humans with positron emission tomography. A two‐step radiosynthetic pathway to prepare fluorine‐18‐labelled ciprofloxacin (1‐cyclopropyl‐6‐[¹⁸F]fluoro‐1,4‐dihydro‐4‐oxo‐7‐(1‐piperazinyl)‐quinoline‐3‐carboxylic acid) has previously been developed. In the present work this approach was applied to the preparation of the structurally related compounds [¹⁸F]norfloxacin (1‐ethyl‐6‐[¹⁸F]fluoro‐1,4‐dihydro‐4‐oxo‐7‐(1‐piperazinyl)‐quinoline‐3‐carboxylic acid) and [¹⁸F]pefloxacin (1‐ethyl‐6‐[¹⁸F]fluoro‐1,4‐dihydro‐7‐(4‐methyl‐1‐piperazinyl)‐4‐oxo‐quinoline‐3‐carboxylic acid). The first step of the radiosynthesis consisted of a ¹⁸F for ¹⁹F exchange reaction on a 7‐chloro‐substituted precursor molecule, followed by coupling reactions with the amines piperazine or 1‐methylpiperazine. Starting from 51–58 GBq of [¹⁸F]fluoride 1.9–2.0 GBq of [¹⁸F]norfloxacin or [¹⁸F]pefloxacin, ready for intravenous injection, could be obtained in a synthesis time of 130 min (3.5–3.8% overall radiochemical yield). Moreover, the preparation of [¹⁸F]levofloxacin ((‐)‐(S)‐9‐[¹⁸F]fluoro‐2,3‐dihydro‐3‐methyl‐10‐(4‐methyl‐1‐piperazinyl)‐7‐oxo‐7H‐pyrido[1,2,3‐de]‐1,4‐benzoxazine‐6‐carboxylicacid) was attempted but failed to afford the desired product in practical amounts. Copyright © 2003 John Wiley & Sons, Ltd.