RESUMO
PURPOSE: Boramino acids are a class of amino acid biomimics that replace the carboxylate group with trifluoroborate and can achieve the 18F-labeled positron emission tomography (PET) and boron neutron capture therapy (BNCT) with identical chemical structure. METHODS: This study reports a trifluoroborate-derived boronophenylalanine (BBPA), a derived boronophenylalanine (BPA) for BNCT, as a promising PET tracer for tumor imaging. RESULTS: Competition inhibition assays in cancer cells suggested the cell accumulation of [18F]BBPA is through large neutral amino acid transporter type-1 (LAT-1). Of note, [18F]BBPA is a pan-cancer probe that shows notable tumor uptake in B16-F10 tumor-bearing mice. In the patients with gliomas and metastatic brain tumors, [18F]BBPA-PET shows good tumor uptake and notable tumor-to-normal brain ratio (T/N ratio, 18.7 ± 5.5, n = 11), higher than common amino acid PET tracers. The [18F]BBPA-PET quantitative parameters exhibited no difference in diverse contrast-enhanced status (P = 0.115-0.687) suggesting the [18F]BBPA uptake was independent from MRI contrast-enhancement. CONCLUSION: This study outlines a clinical trial with [18F]BBPA to achieve higher tumor-specific accumulation for PET, provides a potential technique for brain tumor diagnosis, and might facilitate the BNCT of brain tumors.
Assuntos
Compostos de Boro , Neoplasias Encefálicas , Radioisótopos de Flúor , Fenilalanina , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Traçadores Radioativos , Animais , Feminino , Humanos , Camundongos , Compostos de Boro/análise , Compostos de Boro/metabolismo , Compostos de Boro/farmacocinética , Terapia por Captura de Nêutron de Boro , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Radioisótopos de Flúor/análise , Radioisótopos de Flúor/metabolismo , Radioisótopos de Flúor/farmacocinética , Voluntários Saudáveis , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Imageamento por Ressonância Magnética , Melanoma Experimental , Camundongos Endogâmicos C57BL , Sondas Moleculares/análise , Sondas Moleculares/metabolismo , Sondas Moleculares/farmacocinética , Fenilalanina/análogos & derivados , Fenilalanina/análise , Fenilalanina/metabolismo , Fenilalanina/farmacocinética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A bifunctional silyl reagent Me2(CH2[double bond, length as m-dash]CH)SiCN has been developed as a novel ethylene equivalent for the Diels-Alder (DA) reaction. The use of this reagent enables the controllable synthesis of value-added cyclohexenyl ketones or 2-acyl cyclohexancarbonitrile derivatives through a five- or six-step tandem sequence based on a Wittig/cyanosilylation/DA reaction/retro-cyanosilylation/isomerization sequence that involves a temporary silicon-tethered intramolecular DA reaction.