Preparation of N′₄‐[¹¹C]methyl‐ciprofloxacin for positron emission tomography studies

Abstract

SummaryThe synthesis of N 4 0 -[ 11 C]methyl-ciprofloxacin for pharmacological studies using positron emission tomography is described. The starting material was treated with [ 11 C]methyl iodide at 1208C in DMF for 5 min. After HPLC separation on a C 18 -column with water/ethanol as mobile phase, the [ 11 C]methyl labelled compound was produced with a radiochemical yield of at least 25% (end of synthesis from [ 11 C]CO 2 ). Activities from 1.48 to 2.22 GBq (40 to 60 mCi) were obtained 1 h after the irradiation, ready for intravenous injection. The carrier ranged between 0.05 and 0.08 mmol (0.010-0.016 mmol/ml).

Synthesis of N4′-[18F]Fluoroalkylated Ciprofloxacin as a Potential Bacterial Infection Imaging Agent for PET Study

“…The tert-alcohol media nucleophilic fluorination (25)(26)(27) of precursors 11 and 12 using tetrabutylammonium fluoride (TBAF) proceeded selectively producing the desired fluoro-products in high yields (13, 78%; and 14, 86%, respectively) without intracyclic or alkene byproducts (20,21). N 4 ′-2-Fluoroethyl ciprofloxacin (15) and N 4 ′-3-fluoropropylciprofloxacin (16) were produced by hydrolysis of methyl esters 13 and 14, respectively.…”

“…The residue was purified by flash column chromatography (5% MeOH/CH 2 Cl 2 ) to obtain 76 mg (78%) of N 4 ′-2-fluoroethylciprofloxacin methyl ester (13) as a white solid; 1 H NMR (600 MHz, CDCl 3 ) δ 1.12-1. 15 In Vitro Antibacterial Activity Analysis Studies. The antibacterial activity analysis was determined from the lowest concentration to the high concentration of test compounds that resulted in a complete inhibition of visible growth in the medium.…”

“…However, the chemical structure of 99m Tc-ciprofloxacin has been not determined, and it has been shown to have very low specific activity (6)(7)(8)(9). Since the use of PET as a noninvasive nuclear imaging approach allows the measurement of nano-or picomolar-level concentrations of molecules in the tissues of virtually all organs with higher spatial and temporal resolutions than SPECT (10)(11)(12), many researchers have shown an interest in ciprofloxacin analogues labeled with a positron emitter for PET such as [ 18 F]ciprofloxacin (13), [ 18 F]COPCA (14), and N 4 ′-[ 11 C]methylciprofloxacin (15). However, [ 18 F]ciprofloxacin also has low specific activity (which can decrease PET imaging quality), because it is [ 18 F]radiolabeled via an 18 F-by 19 Fexchange reaction from ciprofloxacin in nature; consequently, it is difficult to prepare and results in poor radiochemical yield (13,16).…”

“…[ 18 F]COPCA was developed to increase specific activity, and this radiotracer has no specific binding to bacteria and is difficult to purify . Due to short imaging time (the short half-life of carbon-11; t 1/2 = 20.4 min), N 4 ′ -[ 11 C]methylciprofloxacin is not preferred as a PET radiotracer for pharmacokinetics analysis , . It is widely accepted that fluorine-18 is the most desirable PET radionuclide due to its ideal physical properties ( t 1/2 = 110 min) .…”

68Ga‐labeled Ciprofloxacin Conjugates as Radiotracers for Targeting Bacterial Infection

“…To the best of our knowledge, there have not been any reports of 68 Ga-labeled ciprofloxacinbased analogs for PET imaging of bacterial infection. Ciprofloxacin derivatives were previously radiolabeled with 18 F and 11 C but in low yields due to cumbersome procedures (19,20). Radiometal chelation of 68 Ga to the known ligands offers simpler, more rapid, and higher radiochemical yields, especially when automated systems are employed (21,22).…”