Search

Green strategies for late-stage fluorination with 18F, in which ethanol and water are the only solvents used throughout the entire radiolabeling process (azeotropic drying, nucleophilic fluorination, purification and formulation), have been developed and applied to the radiosyntheses of a range of radiopharmaceuticals commonly employed in clinical PET imaging. [ABSTRACT FROM AUTHOR]

(−)-[18F]Flubatine was selected for clinical imaging of α4 β2 nicotinic acetylcholine receptors because of its high affinity and appropriate kinetic profile. A fully automated synthesis of (−)-[18F]flubatine as a sterile isotonic solution suitable for clinical use is reported, as well as the first evaluation in nonhuman primates (rhesus macaques). (−)-[18F]Flubatine was prepared by fluorination of the Boc-protected trimethylammonium iodide precursor with [18F]fluoride in an automated synthesis module. Subsequent deprotection of the Boc group with 1-M HCl yielded (−)-[18F]flubatine, which was purified by semi-preparative HPLC. (−)-[18F]Flubatine was prepared in 25% radiochemical yield (formulated for clinical use at end of synthesis, n = 3), >95% radiochemical purity, and specific activity = 4647 Ci/mmol (171.9 GBq/µmol). Doses met all quality control criteria confirming their suitability for clinical use. Evaluation of (−)-[18F]flubatine in rhesus macaques was performed with a Concorde MicroPET P4 scanner (Concorde MicroSystems, Knoxville, TN). The brain was imaged for 90 min, and data were reconstructed using the 3-D maximum a posteriori algorithm. Image analysis revealed higher uptake and slower washout in the thalamus than those in other areas of the brain and peak uptake at 45 min. Injection of 2.5 µg/kg of nifene at 60 min initiated a slow washout of [18F]flubatine, with about 25% clearance from the thalamus by the end of imaging at 90 min. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Review: 257 refs. [ABSTRACT FROM AUTHOR]

PURPOSE: Detection of bacteria‐specific metabolism via positron emission tomography (PET) is an emerging strategy to image human pathogens, with dramatic implications for clinical practice. In silico and in vitro screening tools have recently been applied to this problem, with several monosaccharides including l‐arabinose showing rapid accumulation in Escherichia coli and other organisms. Our goal for this study was to evaluate several synthetically viable arabinofuranose‐derived 18F analogs for their incorporation into pathogenic bacteria. PROCEDURES: We synthesized four radiolabeled arabinofuranose‐derived sugars: 2‐deoxy‐2‐[18F]fluoro‐arabinofuranoses (d‐2‐18F‐AF and l‐2‐18F‐AF) and 5‐deoxy‐5‐[18F]fluoro‐arabinofuranoses (d‐5‐18F‐AF and l‐5‐18F‐AF). The arabinofuranoses were synthesized from 18F‐ via triflated, peracetylated precursors analogous to the most common radiosynthesis of 2‐deoxy‐2‐[18F]fluoro‐d‐glucose ([18F]FDG). These radiotracers were screened for their uptake into E. coli and Staphylococcus aureus. Subsequently, the sensitivity of d‐2‐18F‐AF and l‐2‐18F‐AF to key human pathogens was investigated in vitro. RESULTS: All 18F radiotracer targets were synthesized in high radiochemical purity. In the screening study, d‐2‐18F‐AF and l‐2‐18F‐AF showed greater accumulation in E. coli than in S. aureus. When evaluated in a panel of pathologic microorganisms, both d‐2‐18F‐AF and l‐2‐18F‐AF demonstrated sensitivity to most gram‐positive and gram‐negative bacteria. CONCLUSIONS: Arabinofuranose‐derived 18F PET radiotracers can be synthesized with high radiochemical purity. Our study showed absence of bacterial accumulation for 5‐substitued analogs, a finding that may have mechanistic implications for related tracers. Both d‐2‐18F‐AF and l‐2‐18F‐AF showed sensitivity to most gram‐negative and gram‐positive organisms. Future in vivo studies will evaluate the diagnostic accuracy of these radiotracers in animal models of infection. [ABSTRACT FROM AUTHOR]