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18F Labeling of a new naphthalene derivative as potential Alzheimer Disease PET imaging agent. Synthesis and preclinical studies

AutorFernández-Maza, L. ; Balcerzyk, Marcin ; Fernández-Gómez, Isabel ; Parrado-Gallego, Ángel
Fecha de publicación2015
Resumen[Introduction]: Radiotracers for β-amyloid plaques PET imaging with best results include naphthalene derivative structures. CNEURO has developed and patented some naphthalene derivative molecules for the diagnosis of Alzheimer Disease at early stages (CU/P/2009/57, CU/P/2013/27, EP 2 436 666 A20, South Africa P58243ZA00. A successful 18F-labelling of such molecules by nucleophilic substitution synthesis was developed at CNA, for β-amyloid plaques PET imaging. [Matherial and methods]: 3-(6-methoxy-2-naphtyl)propyl-4-methylbenzenesulphonate was used as precursor for the labelling process. 18F- was obtained from a Cyclone 18/9 MeV cyclotron (IBA, Belgium) and nucleophilic substitution took place in a modified TracerLab FXFN module (GE, USA). Azeotropic distillation was performed at 100°C in vacuum and with helium flushing. Fluorination of precursor took place at 70°C for ten minutes, with subsequent acidic hydrolysis and neutralization using NaOH 1N. The intermediate compound (before hydrolysis) was dried to avoid any presence of acetonitrile (precursor solvent). The radiotracer 2-(3-[18F]fluoropropyl)-6-methoxynaphtalene was purified by solid phase extraction cartridges (SPE), connecting two alumina Sep-Pack and a SCX Sep-Pack to retain unreacted 18F- and cationic impurities. The labeled compound was retained in a C18 Sep-Pack, and eluted in absolute ethanol. The solution of radiotracer was diluted with saline for injection. Quality controls were performed before injection to the animals; pH, absence of particles, and radiochemical purity (RCP). RCP was determined with a Dionex HPLC system and a coupled radiation detector. The stationary phase was a C18 reverse phase analytical column and acetonitrile/water (75/25) as mobile phase. Two transgenic mice APPSwe/PS1dE8 with amyloid plaques and two wild type mice for control were injected with the radiotracer for PET/CT studies. Whole body images of biodistribution were obtained, and kinetic curves of radioactivity at several cerebral regions were performed. [Results]: Radiochemical yield reached 49,8% (uncorrected decay), and radiochemical purity was higher than 95% in all batches. In vitro stability cromatograms demonstrated that 2-(3-[18F]fluoropropyl)-6-methoxynaphtalene is stable for more than ten hours. Comparison between transgenic and control mice was established by cortexcerebellum SUVratio (SUVr) curve. [Conclusions]: Radiosynthesis of 2-(3-[18F]fluoropropyl)-6-methoxynaphtalene by nucleophilic substitution of tosyl group at the precursor gives good radiochemical yields and radiochemical purity higher than 95%, which makes the radiotracer useful for brain β-amyloid PET imaging. Its in vitro stability (more than 10h) allows several patient studies from the same batch. PET/CT studies show that 2-(3-[18F]fluoropropyl)-6-methoxynaphtalene crosses blood brain barrier, with higher brain uptake in transgenic mice, in comparison with control animals.
DescripciónResumen del póster presentado al 28th Annual Congress of the European Association of Nuclear Medicine (EANM), celebrado en Hamburgo (Alemania) del 10 al 14 de octubre de 2015.-- et al.
Aparece en las colecciones: (CNA) Comunicaciones congresos
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