Discovery of 7‑[18F]Fluorotryptophan as a Novel Positron Emission Tomography (PET) Probe for the Visualization of Tryptophan Metabolism in Vivo

Tryptophan and its metabolites are involved in different physiological and pathophysiological processes. Consequently, positron emission tomography (PET) tracers addressing tryptophan metabolic pathways should allow the detection of different pathologies like neurological disorders and cancer. Herein we report an efficient method for the preparation of fluorotryptophans labeled in different positions with 18F and their biological evaluation. 4–7-[18F]­Fluorotryptophans ([18F]­FTrps) were prepared according to a modified protocol of alcohol-enhanced Cu-mediated radiofluorination in 30–53% radiochemical yields. In vitro experiments demonstrated high cellular uptake of 4–7-[18F]­FTrps in different tumor cell lines. 4, 5-, and 6-[18F]­FTrps, although stable in vitro, suffered from rapid in vivo defluorination. In contrast, 7-[18F]­FTrp demonstrated a high in vivo stability and enabled a clear delineation of serotonergic areas and melatonin-producing pineal gland in rat brains. Moreover 7-[18F]­FTrp accumulated in different tumor xenografts in a chick embryo CAM model. Thus, 7-[18F]­FTrp represents a highly promising PET probe for imaging of Trp metabolism.

色氨酸(Tryptophan)及其代谢产物参与多种生理与病理生理过程。据此，靶向色氨酸代谢通路的正电子发射断层显像(PET)示踪剂，可用于检测神经系统疾病、癌症等多种病理状态。本文报道了一种氟-18(¹⁸F)位点特异性标记氟代色氨酸的高效制备方法，及其生物学评价研究。本研究通过改良的醇促铜介导放射氟化方案，制备得到4~7位[¹⁸F]标记的氟代色氨酸([¹⁸F]­FTrps)，放化产率可达30%~53%。体外实验结果显示，该系列标记物在多种肿瘤细胞系中均表现出较高的细胞摄取水平。其中，4、5及6位[¹⁸F]­FTrps虽体外稳定性良好，但在体内会发生快速脱氟反应。与之相反，7位[¹⁸F]­FTrp展现出优异的体内稳定性，可清晰区分大鼠脑中的血清素能区域与分泌褪黑素的松果体。此外，在鸡胚CAM模型中，7位[¹⁸F]­FTrp可在多种肿瘤异种移植物中富集。综上，7位[¹⁸F]­FTrp是一款极具应用前景的PET探针，可用于色氨酸代谢的影像学检测。