Study Of PET/MRI Dual Targeted Molecular Probes For Early Diagnosis Of Lung Cancer

Lung cancer is the leading cause of cancer-related death in the world.The reason is that there is no obvious signs or clinical symptoms of early lung cancer so that it is easy for us to ignore the disease.And early diagnosis and treatment are the key to improve the prognosis of lung cancer.Therefore,the study of the early diagnosis of lung cancer has became more and more important in clinical development,and how to address this problem and achieve early diagnosis is a difficult and significant medical challenge.In this study,based on the preparation of ultra-small size iron oxide nanoparticles?USPIO?,we conjugated small RGD peptide?targeting the early?v?3 receptor of non-small cell lung cancer?and GE11 small peptide?targeting the EGFR receptor?to the nanoparticles,and positron-emitting radionuclide-18 were labeled on nanoparticles to construct PET/MRI dual-modality nano-probes,which were capable of specifically targeting non-small cell lung cancer cells.Then we explore the possibility of the probes'specificity and possibility in the early diagnosis of lung cancer.Under the premise of the preparation of superparamagnetic iron nanomaterials,we added dopamine coating and surface modification of polyethylene glycol?PEG?to increase the biocompatibility and hydrophilicity,and then used the“click chemistry”method to couple the RGD peptides?Arg.Gly.Asp?and GE11 peptides?YHWYGYTPQNVI?to the particle surface,next,we coupled fluorine-19 to the surface so we obtained two single-targeting(¹⁸F-RGD@USPIO?¹⁸F-GEll@USPIO)and one dual-targeting probes(¹⁸F-GE11-RGD@USPIO).Then,we studied the probes'in vitro properties such as stability,cytotoxicity and specificity as well as relaxivity.At the same time,a labeling platform that can achieve rapid labeling of fluorine-18 nuclide were built successfully,and we used the click chemistry method to achieve the labeling of fluorine-18 nuclide.MRI imaging and PET imaging were performed respectively,and image analysis was performed to evaluate the use of probes in the early diagnosis of lung cancer.Finally,immunohistochemistry and Prussian blue staining of the tumor tissue were used to verify the aggregation effect of the probe in the tumor and the expression level of the receptor.The main results of this study include:the construction of nanoparticle probes which can target both the?v?₃ receptor and the EGFR;And the small peptide coupling efficiency were high?95%-98%?.In vitro experiments showed that the probes has good stability and low cytotoxicity;In vivo MRI imaging of two single-targeting probes and one dual-targeting probes showed that all three probes were accumulated in the tumor site and had good T₂ contrast effect,and showed the superiority of dual target targeting Diagnostic performance;The click chemistry method we used for ¹⁸F modular labeling achieved good PET-CT imaging,and the results showed that probes of the target group were higher than the control group and the blocking group in mouse tumor site.Immunohistochemical analysis of the tumor showed that both EGFR and?v?₃receptors in H1299 lung cancer tissues were highly expressed,while Prussian blue staining experiments also verified that the accumulation of the probe at the tumor site indicates that the probes have good specificity.