Development Of ¹⁸F-labeled Ultra-small Rare Earth Nanoparticles Probes And Its Application In Pharmaceuticals Tracing In Vivo

Positron Emission Computed Tomography（PET）is an important technology in pharmaceutal research,especially the nano-drug in vivo distribution because of its high sensitivity,unlimited detection depth and accurate quantitative detection.The commonly used scheme is to label 18F which has a short half-life directly on the nano-drug.The labeling process is usually complicated and the 18F labelled nano-drug can only be detected in a short time after injection,which is not suitable for long-circulating nano-drug detection after injection for more than 8 hours.Based on bio-orthogonal reaction,fluorine 18/tetrazine labeled ultra-small size rare earth nanoparticle probe(¹⁸F@NaGdF₄-Tz)was developed,and trans-cyclooctene modified gold nanoparticles（Au NP-TCO）was used as a model drug to verify the probe.Firstly,oleic acid modified rare earth nanoparticles（NaGdF₄-OA）were prepared by pyrolysis.After surface modification by L-cysteine and Tz-PEG₅-NHS in turn,NaGdF₄-Tz was prepared.After incubated with fluoride 18 ion solution and later purification,¹⁸F@NaGdF₄-Tz was prepared.Secondly,citric acid modified 100 nm gold nanoparticles were prepared.After surface modification with SH-PEG₄-NH₂ and TCO-PEG₄-NHS,Au NP-TCO was prepared.Thirdly,in the bio-orthogonal experiments in vitro and in vivo,the energy spectrum and PET imaging results confirm the binding stability of 18F@NaGdF₄-Tz and Au NP-TCO in physiological environment.Finally,after tail vain Au NP-TCO injection for a while,¹⁸F@NaGdF₄-Tz was injected into the same nude mice bearing tumors.The PET imaging results confirm that ¹⁸F@NaGdF₄-Tz can successfully monitor the long-circulating Au NP-TCO in real time,which lays a foundation for real-time tracing and quantitative analysis of nano-drugs in the future.