Application Of Photoacoustic Imaging Combined With Molecular Application Of Photoacoustic Imaging Combined With Molecular Irregular Hepatectomy

Background:Hepatocellular carcinoma is one of the most common malignant tumors,which is associated with hepatitis virus infection,alcoholic cirrhosis and other factors.At present,surgery remains the preferred treatment for HCC.Routine hepatectomy based on anatomical description has been widely accepted by hepatobiliary surgeons since the mid-1950s,but in clinical practice,a large number of patients cannot tolerate extensive anatomical hepatectomy for various reasons.Therefore,irregular hepatectomy has emerged.Although the scope and advantages of anatomic hepatectomy and irregular hepatectomy remain controversial,there is a general consensus that irregular hepatectomy is the treatment of choice for patients with severe cirrhosis,severe residual liver volume deficiency,and small local hepatic metastases.In irregular hepatectomy,the liver is not resected according to the anatomical range of liver lobes or liver segments,but the local liver is resected irregularly around the tumor lesion,which makes it particularly important to determine the intraoperative boundary of the tumor and clear the safe resection range.The application of precise irregular hepatectomy depends largely on the ability to define the boundaries of the intraoperative tumor,which will optimize the accuracy,efficacy,safety,and minimally invasive of the surgical procedure.Therefore,there is an urgent need for a fast,sensitive,high-resolution and high-specificity imaging method to define intraoperative tumor boundaries.Purpose:Currently,there are limited tools available for the effective identification of tumor boundaries in irregular hepatectomy.Photoacoustic imaging combines the characteristics of optical imaging and acoustic imaging,which has high resolution,high sensitivity and high penetration depth.By converting the approved investigational drug 18F-Alfatide into small molecule probe IR820-E[c(RGDfK)]2,we hope to combine multi-spectral photoacoustic imaging with targeted small molecule probe to more accurately define the intraoperative tumor boundary,so that it can be transformed into a clinical application method of guided precise irregular hepatectomy.Experimental design:Firstly,a small molecular probe IR820-E[c(RGDfK)]2 targeting integrin ?v?3 was designed,synthesized and characterized.Secondly,the probe was studied in vitro to determine its optical properties,affinity,specificity and biocompatibility.The pharmacokinetic properties and biosafety of the probe were evaluated.The best imaging time point and contrast of multispectral photoacoustic imaging were defined.Multispectral photoacoustic imaging guided subcutaneous tumor resection and irregular liver resection were performed.Finally,the IR820-E[c(RGDfK)]2 staining was performed on the in vitro macroscopic 3 D photoacoustic imaging of liver cancer surgical specimens.Results:The targeted small molecule probe IR820-E[c(RGDfK)]2 has the advantages of simple synthesis,photostability and biocompatibility.It has strong affinity and specificity for integrin ?v?3,and has good pharmacokinetic properties and biosafety.Combined with the multispectral photoacoustic imaging technique,the probe can effectively distinguish the tumor tissue from the normal liver tissue.In subcutaneous tumor resection and irregular hepatectomy,preoperative tumor localization,intraoperative tumor boundary precise delineation and navigational tumor complete resection were successfully accomplished.In the study of 3D photoacoustic imaging of human liver cancer specimen,targeted small molecule probe IR820-E[c(RGDfK)]2 can effectively target and develop liver cancer tissue,and can accurately and clearly display the boundary of tumor region.Conclusions:The combination of targeted small molecule probe IR820-E[c(RGDfK)]2 with multispectral photoacoustic imaging technology is expected to be an effective auxiliary tool for irregular hepatectomy in future clinical work.