An Experimental Animal Study Of ⁶⁸Ga-HBED-CC-Lys-CO-Glu On Prostate Cancer Target Imaging

Object:To study the labeling method of Glu-CO-Lys(Ahx)-[68Ga(HBED-CC)].And investigate the metabolic kinetics of the agency.And reveal the potential value of 68Ga-HBED-CC-Lys-CO-Glu in prostate cancer target imaging.Method:1)To investigate and establish 68Ga-HBED-CC-Lys-CO-Glu labeling methods.Study the radiochemistry purity and stability in vitro by High Performance Liquid Chromatography(HPLC).In addition,the affection towards product of react condition was also disused by HPLC.2)The biodistribution and kinetics were evaluated by the dissection method and dynamic imaging with Micro PET in normal ICR mice.The affection of react condition to pharmacokinetics was studied based on data of Micro PET.3)PSMA positive cell line of prostate cancer,22RV1,and PSMA negative cell line,PC-3,was used to examine the specific of 68Ga-HBED-CC-Lys-CO-Glu on cell level.The animal model of 22RV1 and PC-3 was established.The targeting of image agency was investigate by Micro PET.And relevance between SUVmean and expression of PSMA was proved by histologyResult:1)The optimal labeling conditions of 68Ga-HBED-CC-Lys-CO-Glu:185?555 MBq GaCl3 in the 4 ml was added 5?g of HBED-CC-Lys-CO-Glu at pH = 4.HPLC show the bimodal product.Radiochemical purity was calculated by combining with duo-peak,radiochemical purity was(95±2)%at 2h,and the ratio of the two peaks at different temperatures by significantly affected.2)Dynamic Micro PET reveal drugs was metabolized by renal principally;and rapid blood clearance was observed.Different synthesis conditions exist on the pharmacokinetic parameters.Under heating conditions,it is more conducive to the excretion of drugs.Biodistribution results coincide with the results of dynamic imaging.3)Cell experiments confirmed 68Ga-HBED-CC-Lys-CO-Glu specific to 22RV1 cell line.Micro PET imaging revealed 22RV1 tumor-bearing mice tumor uptake was significantly higher than PC-3 tumor-bearing mice.The expression level of PSMA collaborated with SUVmean proved by linear correlation analysis with R2 =0.9346.Conclusion:1)68Ga-HBED-CC-Lys-CO-Glu has appreciated pharmacokinetic properties;and synthesis under heating conditions can accelerate their drug excretion.Fast blood clearance of drugs was observed.It was proved that the kidneys are mainly excretion organ.2)68Ga-HBED-CC-Lys-CO-Glu excellent targeting towards PSMA positive tumor.And be able to reflect the level of expression of PSMA tumor.