| Objectives:To explore the method of radiolabeling lipiodol with 188Re and to appraise the quality of the product.; To investigate the distribution ,therapeutic effect of 188Re-lipiodol in bearing cancer S180 mice. To analyze the joint action of LDR with internal-radiation therapy.Methods:①Lipiodol was labeled with 188Re directly at the temperatures from 75℃to 120℃with different reaction conditions. The labeling efficiencies at the different time after label were measured to evaluate the stability of 188Re-lipiodol;②The molecular structure change caused by radiolabeling was analyzed with infrared spectrometer;③The embedding effect of lipiodol was explored by SPECT imaging with Kunming mice bearing S180 sarcoma .④188Re-lipiodol with the dose of 37MBq/kg was intratumourally injected into 40 Kunming mice bearing S180 sarcoma. The animals are sacrificed at 1h,4h,8h,12h,24h,36h,48h,60h after injection. The heart, lung, kidney and other organs were taken, weighed and radioactivities were counted with a gamma scintillation counter.⑤140 Kunming mice bearing S180 sarcoma were random divided into 7 groups : control group,188ReO4- group,paclitaxel group (15mg/kg thrice,quaque die alterna),therapeutic alliance(paclitaxe and midst dose internal-radiation therapy ) group,low dose internal-radiation therapy group(intratumourally injection of 0.1 ml 188Re—lipiodol 3.7kBq/mouse,148kBq/kg ),midst dose internal-radiation therapy group ( intratumourally injection of 0.1ml 188Re—lipiodol 18.5kBq/mouse,740kBq/kg),high dose internal-radiation therapy group(intratumourally injection of 0.1ml 188Re—lipiodol 37kBq/mouse,1480kBq/kg ). The tumor volumes were measured at the different time after treatment and the tumor pathological change and apoptosis morphology were observed by light microscope and laser confocal microscopy,respectively. The survival times of mice were recorded and analysed by SPSS 13.0.⑥80 Kunming mice bearing S180 sarcoma were random divided into 4 groups : control group,internal-radiation therapy group(intratumourally injection 0.1ml 188Re—lipiodol 18.5kBq/mouse,740kBq/kg),LDR group,therapeutic alliance(LDR and internal-radiation therapy)group.Results :①The optimal condition was obtained with the labeling efficiency over 99.1±0.4%;More than 90.9±1.9% and 92.8±1.2% of radioactivity was kept in lipidol form at room temperature and in 37℃human plasma for 3 days ;②Infrared spectrum showed that the molecular structure of radiolabeled lipiodol wasn't changed;③SPECT imaging of mice bearing S180 tumor testified the radioactivity concentrated in tumor for 48h after injection of 188Re-lipiodol.④Biodistribution of mice showed that radioactivities mainly accumulated in tumor from 1h to 60h after intratumourally injection. The peak value (300.81±50.16)of %ID/g appeared at 24h after injection.⑤Tumor pathological section showed that tumor cellular necrosis and nucleus condense appeared in high dose internal-radiation therapy group,therapeutic alliance(paclitaxe and midst dose internal-radiation therapy)group. Tumor cellular swelling and tumor cellular necrosis were observed in paclitaxel group, while no tumor cellular necrosis and much tumor cell caryocinesis were obsrved in control group. The inhibition rates of tumor are as follows: high dose internal-radiation therapy group:84.90%,therapeutic alliance(paclitaxe and midst dose internal-radiation therapy)group :71.04%,midst dose internal-radiation therapy group:64.19%,188ReO4- group :57.94%,chems group:23.70%. The tumor volume of low dose internal-radiation therapy group is bigger than that of control group. The apoptosis rate are as follows: control group:3.01±1.78(%), low dose internal-radiation therapy group 10.44±3.56(%),paclitaxel control group: 26.52±6.11(%),midst dose internal-radiation therapy group :31.42±6.66(%),high dose internal-radiation therapy group :34.66±2.88(%),therapeutic alliance(paclitaxe and midst dose internal-radiation therapy)group :39.69±5.21(%),There are significant differences between the groups with p<0.01. Comparing the differences of prolonged survival period of mice bearing S180 sarcoma between the groups of high dose internal-radiation therapy,therapeutic alliance ( paclitaxe and midst dose internal-radiation therapy ),midst dose internal-radiation therapy remarkably with the P<0.01.⑥The inhibition rates of tumor after treatment for 18d are as follows:internal-radiation therapy :64.19%(p<0.05),therapeutic alliance (LDR and internal-radiation therapy )74.21%(p<0.01),LDR:41.08%(p>0.05). The apoptosis rates are : LDR group: 24.75±4.98(%),therapeutic alliance (LDR and internal-radiation therapy ):41.71±3.51(%),(P<0.01). Survival periods of mice bearing S180 sarcoma between internal-radiation therapy,therapeutic alliance (LDR and internal-radiation therapy ) groups show the significant differance(P<0.01), while there is no obvious difference between LDR group and blank control group(p>0.05).Conclusion: The direct radiolabeling method was easy to operate with the labeling efficiency of higher than 99.1±0.4% and the radiolabeled product was stable for 72h, SPECT imaging of mice bearing S180 tumor testified the radioactivity concentrated in tumor for 48h after injection of 188Re-lipiodol. 188Re-lipiodol can be retained within the tumour tissue and the tumor cells can be killed. Significant prolonged survival period of mice bearing S180 sarcoma was detected. LDR can be used for increase the kill effect of 188Re-lipiodol on tumor cells.
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