Tumor Pretargeted Positron Emission Tomography Imaging Based On Two Kinds Of Nanoparticl Probes With Different PK

Positron Emission Tomography?PET?is one of the most mature and sensitive tumor diagnosis techniques.Highly specific and sensitive probes are essential for the PET based tumor diagnosis.While ¹⁸F-FDG which has been most commonly used in clinical is not a tumor-specific imaging agent.Therefore,the development of new PET imaging probe that could specifically enriched in the tumor has become the focus of nuclear medicine research.In this study,we designed and prepared two kinds of nanoparticle imaging probes with different PK and function for rapid aqueous 18F labeling and high contrast tumor pre-targeting PET imaging.At first,we synthesized and purified two self-assembled molecular modules Ad-PEG-TCO and CD-PEI.Long-circulating self-assembled nanoparticle were prepared by mixing Ad-PEG-TCO,Ad-PAMAM and CD-PEI based on the molecular recognition of adamantane and cyclodextrin.The morphology,cytotoxicity and stability of nanoparticles were investigated.Meanwhile,ultra-small rare earth nanoparticles were prepared by using solvothermal method,and then converted into hydrophilic for further tetrazine modify.The obtained rare earth nanoparticles were labeled with radioisotope ¹⁸F based on its high ¹⁸F absorbability.The cytotoxicity and pharmacokinetic of ¹⁸F labelled nanoparticles were investigated.Finally,these two kinds of nanoparticles with different PK and function were used for tumor pretargeting PET imaging.The results shown that the self-assembled nanoparticle at 150nm size have good stability and low cytotoxicity.It can achieve the passive tumor-pretargeting effect based on the EPR effect,meanwhile providing bio-orthogonal module that reacts with radioactive imaging group.The ultra-small rare-earth nanoparticles can labelled with radioisotope F¹⁸efficiently and quickly.The obtained ¹⁸F@NaGdF₄-Tz could be eliminated from the body by rapid and efficient urinary excretion.In tumor pretargeting PET imaging test,the ¹⁸F@NaGdF₄-Tz was detained in the tumor tissue through reacting with tumor pre-targeted TCO-SNPs,while free ¹⁸F@NaGdF₄-Tz nanoparticles were cleared by urinary excretion rapidly,then high signal-to-noise PET imaging of tumor was obtained.In conclusion,we successfully prepared two kinds of nanoparticles with different PK and function and developed a tumor pre-targeting PET imaging strategy based on these two probes.High sensitivity and tumor-to-background tissue contrast PET imaging was achieved by circumventing limitations such as hard ¹⁸F labeling and probes'pharmacokinetic.