Application Research Of Optical Molecular Imaging In The Diagnosis And Treatment Of Malignant Tumors

Background:Cancer is one of the leading lethal diseases worldwide,early diagnosis and effective treatment are the keys to improve the prognosis of patients.At present,image-guided interventional treatment,such as radiofrequency ablation has become one of the common treatment methods for solid tumors in addition to the traditional treatment methods,such as surgical and chemoradiotherapy.However,for some tumors,such as pancreatic cancer,early specific diagnosis is still the difficulty of clinical work.And thermal ablation also has some unresolved problems,such as local reccurence in some patients after surgery.Optical molecular imaging has the advantages of high sensitivity and specificity,and great progress has made in tumor diagnosis and intraoperative guidance.In particular,utilizing the near-infrared fluorescent molecular probe expands its clinical application prospect.Objectives:To develope molecular-targeted near-infrared fluorescent probes,and investigate the value of optical molecular imaging in diagnosing malignant tumors and guiding thermal ablation in the treatment of malignant tumors.Methods:1.Molecular imaging study of tumor specific diagnosis based on targeted optical probe（1）To synthesise type 2 cannabinoid receptor（CB₂R）-targeted near-infrared fluorescent molecular probes（NIR760-XLP6）,and perform fluorescent imaging in pancreatic cancer cells.（2）To establish pancreatic cancer subcutaneous xenograft tumor mouse model and lymph node metastasis model,perform optical imaging in vivo and ex vivo,and observe the tissue distribution and metabolism of probes.2.Molecular imaging study of real-time guided tumor ablation based on targeted optical probe（1）To synthesise integrinα_vβ₃-targeted thermally sensitive fluorescent molecular probes（RGD-Cy5-R-PE）,and perform fluorescent imaging in tumor cells.（2）To establish hepatic cancer subcutaneous xenograft tumor mouse model,perform radiofrequency ablation guided by optical imaging in vivo,and observe the changes of fluorescent intensity in tumor areas with different ablation temperature.Results:（1）NIR760-XLP6 could specifically bind to CB₂R overexpressed in tumor cells.（2）NIR760-XLP6 specifically bind to CB₂R overexpressed in tumors,and could be used for optical molecular imaging of in-situ tumors and metastatic lymph nodes.（3）RGD-Cy5-R-PE could specifically bind to integrinα_vβ₃ overexpressed in tumor cells,and its fluorescent intensity decreased with the increase of temperature.（4）The fluorescent intensity of RGD-Cy5-R-PE in tumor areas decreased with the increase of ablation temperature.Conclusions:Optical molecular imaging,utilizing molecular-targeted near-infrared fluorescent probes,has great potential in clinical application in the diagnosis of malignant tumors and guidance during thermal ablation.