Pretherapy Study On Endovascular Administration Of Rhenium-188 Labeled Drug In Rabbit VX₂ Liver Tumor Model

PartⅠEstablishment of a Rabbit Model Bearing VX2 Liver Tumor and its CT,DSA ManifestationObjective To establish a rabbit model of VX2 liver tumor for experimental study, with pieces of VX2 tumor tissue implanted into the left lobe of the rabbit liver via percutaneous puncture under the guide of CT. and to study the CT,DSA imagining features of the liver tumor.Methods 136 New Zealand white rabbits were established models of VX2 liver tumor via percutaneous puncture under the guide of CT . The death rate of rabbit and the success rate of establishing VX2 liver tumor model was counted respectively. The CT,DSA imagining manifestation of the VX2 liver tumor was analyzed. 5 rabbit models bearing VX2 liver tumor were selected to observe the biological features of tumor by histopathology and microscope photographs.Results Within three weeks after implantation, 21 rabbits were died, The death rate was 16.7%(21/136), and the success rate of establishing VX2 liver tumor model was 75.0% ( 102/136), except for 13 rabbits without liver tumor. The CT,DSA imagining of tumor indicated that the tumor had liberal blood supply of hepatic artery. The liver tumor of 5 rabbit models were confirmed by pathology.Conclusion It's a new method to establishing a rabbit model of VX2 liver tumor with pieces of VX2 tumor tissue implanted into the left lobe of the rabbit liver via percutaneous puncture under the guide of CT. The CT,DSA imagining show that the tumor is hypervascular. The rabbit model bearing VX2 liver tumor is more suitable for endovascular interventional experimental study.PartⅡThe preparation of 188Re labelled Lipiodol, MAA, stannous sulfur colloidObjective To study the methods for labeling lipiodol, macroaggregated albumin(MAA), and stannous sulfur colloid with rhenium-188.Methods①Lipiodol was labeled with 188Re directly at the temperatures from 75℃to 120℃with different reaction conditions. The time-variation labeling efficiency was measured to evaluate the stability of 188Re-lipiodol.②Macroaggregated albumin(MAA)was labeled with 188Re after extra adding stannous chloride into commercial MAA kit, The time-variation labeling efficiency was measured to evaluate the stability of 188Re-MAA.③Different amount of stannous chloride and sodium thioslphate were respectively added into commercial sulfur colloid (SC). Their labeling efficiencies and the in vitro stabilities were tested.Results①The optimal condition was obtained with the labeling efficiency over 99.11±0.22% at 120℃. More than 90.9±1.9% and 92.8±1.2% of radioactivity was kept in 188Re-lipidol form in room temperature and in 37℃human plasma for 72 hours;②At the condition of additional dosage of 0.5ml stannous chloride(20mg/ml), the labeling efficiency of 188Re-MAA reached(99.64±0.09)%, and(92.53±1.20)% of labeling efficiency was kept in human plasma for 72 hours③At the condition of additional dosage of 0.5ml stannous chloride(20mg/ml) and 0.25ml sodium thioslphate (8mg/ml), the labeling efficiency of 188Re-SC(Sn) reached(98.39±2.66)%, and labeling efficiency was (93.62±0.64)% in the solution (suspending SC to saline=1:10) in room temperature at 72h after preparation. Conclusion The methods for labeling lipiodol, macroaggregated albumin(MAA), and stannous sulfur colloid with rhenium-188 are convenient,and stable in vitro with higher labeling efficiency, which can potentially be the new radiopharmaceuticals used for the treatment of stereo tumor.PartⅢThe Biodistribution after Endovascular Injection of Rhenium-188 Labeled Drugs in Rabbit VX2 Liver Tumor ModelObjective To investigate the biodistribution property of rhenium-188 labeled drug after transcatheter arterial injection of rhenium-188 labeled lipiodol, rhenium-188 labeled macroaggregated albumin(MAA), and rhenium-188 labeled stannous sulfur colloid in rabbit VX2 liver tumor model.Methods 64 rabbits bearing liver tumor were performed transcatheter hepatic arterial injection of lipiodol (group A), Na188ReO4 solution (group B), rhenium-188 labeled lipiodol (group C), rhenium-188 labeled MAA (group D),and rhenium-188 labeled stannous sulfur colloid(group E), respectively. The rabbits in group B,C,D and E were accepted SPECT, then sacrificed at the time of 1h or 24h after administration . Samples of brain, heart, lung, liver, spleen, kidneys, intestine, muscle, blood, and tumor were taken, weighed and measured for radioactivity. The radioactivity of tissue was expressed as percentage of the injected dose per gram of wet tissue weigh(%ID/g). The ratios of tumor to liver, kidneys, muscle, blood, lung were calculated. The ALT,AST and UREA of each of rabbit were detected before and at the time of 1h,24h after administration, respectively.Results 35 rabbits were accepted endovascular administration, and accomplished in the study. The SPECT imaging of 23 rabbits (group C, n=6; group D, n=9; group E, n=8) shew that radioactivity was accumulated in tumor at the time of 1h or 24h after administration. The biodistribution of rhenium-188 labeled drug shew that higher radioactivities uptake were in tumor, liver and kidneys, lower radioactivities uptake were in intestine, heart, brain and muscle. and radioactivities uptake were moderate in lung, blood, and spleen. Radioactivities were decreased as the time passed. The uptake of radioactivity in tumor was higher than in the other tissues. The ratios of T/NT (tumor/ liver, tumor/ kidney, tumor/ lung, tumor/ blood, and tumor/muscle) in each group were compared. There were statistics differences among group B,C,D and E(p<0.05)each other. Except for group C, the differences of the ratio of tumor/ liver were significant between the time of 1h and 24h after administration in group D and E(p<0.05). In each group, the levels of ALT and AST even rose to the highest at the time of 24h after administration, and the amplitude in group B was the smallest. There were no statistics differences among group A,C,D and E(p>0.05), and the differences were significant between group B and group A,C,D,E(p<0.05), respectively. There were statistics differences between the both of the different time, too. In each group, the levels of UREA weren't obviously changed.Conclusion After transcatheter arterial administration, rhenium-188 labeled lipiodol, rhenium-188 labeled MAA, rhenium-188 labeled stannous sulfur colloid has better tumour affinity and retainable accumulation characteristics in tumor which can potentially be the new radioactive agents used for endovascular treatment of liver cancer.