| 1.Studies on inhibition effect of 188Re labeled insulin-like growth factor 1 analogue on human pancreatic carcinoma cell Patu8988The insulin-like growth factor 1 contributes to the development and progression of many tumours. Its receptors overexpress on the membrane of many cells such as pancreatic carcinoma cell. Competing with insulin-like growth factor 1, the insulin-like growth factor 1 analogue can combine with the insulin-like growth factor 1 receptors, and then induce the cancer cells apoptosis. Rhenium-188 (Emax=2.12 Mev) is an attractive radionuclide for radiotherapy due to its high-energyβ-particle emission andγ-emission. The range ofβ-particles emitted by 188Re is 12mm, and 188Re decays with aγ-emission, which allows tumor imaging during therapy. The insulin-like growth factor 1 analogue labeled with 188Re is expected to be a practical radiopharmaceutical, and its biodistribution in nude mice can be seen by scintigraphy imaging.Objective:To study the inhibition effect of 188Re-IGF-1A on the growth of human pancreatic carcinoma cell Patu 8988 in vitro.Methods:①To label IGF-1A with 188Re directly and determine the labeling efficiency .②Patu8988 cell were seeded onto 96-well plate at logarithmic growth phase, and were divided into blank control group, IGF-1A group (1μg,5μg,10μg,20μg), 188ReO4- group(0.37MBq,1.85MBq,3.7MBq,7.4MBq), 188Re-IGF-1A group(0.37MBq,0.74MBq,1.85MBq).③The proliferation inhibition effect of IGF-1A group and 188ReO4- group on cell growth was detected by MTT test at 2d,4d and 6d after administration, The proliferation inhibition effect of 188Re-IGF-1A group was detected by MTT each day for 1 week, and inhibition rates were calculated.④To draw cell growth curve according to the optical density and calculate their inhibition rates. Results:①The labeling efficiency of 188Re-IGF-1A was (94.07±0.32)%.②Patu8988 cells entered the logarithmic phase in the first 4 days and reached the platform on the 4th day, then they decreased on the 6th day.③The difference of OD was always significant (P<0.01) between control group and 188ReO4- group. On the 6th day , OD was 0.588±0.139 in 0.37MBq group,0.325±0.178 in 1.85MBq group,0.292±0.101 in 3.7MBq group, 0.177±0.048 in 7.4MBq group. On the 6th day, inhibition rates was(74.26±5.26)% in 0.37MBq group, (85.90±7.23)% in 1.85MBq group, (87.12±4.63)% in 3.7MBq group,(92.23±1.89)% in 7.4MBq group. The difference of OD and inhibition rates was significant (P < 0.05) between 0.37MBq group and 1.85MBq group,3.7MBq group,7.4MBq group, so was the difference of OD between 1.85MBq group and 7.4MBq group.According analysis of correlation, the Pearson's correlation coefficient of dose and inhibition rates was 0.712 (P=0.00) on the 6th day.④The difference of OD was always significant (P<0.01) between control group and IGF-1A group. On the 2th and 4th day ,the difference of OD and inhibition rates was significant (P<0.05) between 20μg group and 1μg group,5μg group,10μg group. The ratio of inhibition rates in the 20μg group and 1μg group was 2.21 on the 2th day. According analysis of correlation, the Pearson's correlation coefficient of dose and inhibition rates was 0.843 (P=0.00) on the 2th day and 0.447(P=0.02) on the 4th day.⑤The difference of OD and inhibition rates was always significant (P<0.01) between control group and 188Re-IGF-1A group, so was the difference of OD and inhibition rates between 1.85MBq group and 0.37MBq group,0.74MBq group. On the 6th day .Inhibition rates was(93.77±1.12)% in 1.85MBq group. Cells in the 188Re-IGF-1A group grew slower. According analysis of correlation, the Pearson's correlation coefficient of dose and inhibition rates was 0.907 (P=0.00) on the 2th day, 0.874(P=0.00) on the 4th day and 0.817(P=0.00) on the 6th day.⑥Inhibition rates of 188Re-IGF-1A group were always higher than 188ReO4- group and IGF-1A group,and the difference was significant (P < 0.05). The largest ratio of inhibition rates in the 188Re-IGF-1A group and 188ReO4- group was 9.53 in the 1.85MBq group on the 2th day. The largest ratio of inhibition rates in the 188Re-IGF-1A group and IGF-1A group was 1.96 in the 5μg group on the 2th day.Conclusions: 188Re -IGF-1A can inhibit human pancreatic carcinoma cell Patu 8988, and its effect depends on the dose and concentration of 188Re -IGF-1A. It has lager inhibition effect than 188ReO4- and IGF-1A of equal dose. So 188Re-IGF-1A is expected to be used for therapy of human pancreatic carcinoma.2.Studies on biodistribution and imaging of 188Re labeled insulin-like growth factor 1 analogue in nude mice bearing human pancreatic carcinomaObjective:To evaluate the biodistribution and planar SPECT camera imaging characteristics of 188Re-IGF-1A in tumor-bearing mice .Methods:①To establish nude mice model which bearing human pancreatic carcinoma cell Patu 8988 .②To scan normal nude mice at 15min,1h,2h after injection throμgh tail vein with 188Re-IGF-1A. To measure the radioactivity count of different organs, and calculate their percentages of injected dose per gram tissue (%ID/g).③To scan those nude mice at 15min,1h,4h,1d,3d and 5d after intratumor injection with 188Re-IGF-1A,④To scan those nude mice at 15min,1h,2h,4h and 24h after intratumor injection with 188ReO4-, To measure the radioactivity count of those organs and tumors , and calculate the tumor to normal tissue ratio ( T/NT) and the percentages of injected dose per gram tissue (%ID/g) of different organs.Results:①188Re-IGF-1A was major distributed in kidneys, livers, and spleens after injection throμgh tail vein. The uptake was(18.46±1.73)%ID/g in kidneys, (3.94±0.74) %ID/g in livers,(2.48±0.60)%ID/g in spleens at 2h after injection.②188Re-IGF-1A was major distributed in kidneys, livers, and spleens after intratumor injection. The uptake was(25.57±4.27)%ID/g in kidneys, (2.56±2.27) %ID/g in livers,( 1.34±0.86)%ID/g in spleens, (30.02±9.49) %ID/g in livers at 15min after injection.The largest uptake of tumors was(42.38±17.82)%ID/g at 4h after injection of 188Re-IGF-1A. Then the tumor to normal tissue ratios increased and the largest tumor to muscle ratio was 6531.79±4930.26 at 5d after injection.③188ReO4- was major distributed in thyroid glands, stomachs, tumors and blood in nude mice after injection at first.Then %ID/g decreased rapidly in tumors. The largest uptake of stomachs was(24.31±12.48)%ID/g at 1h after injection. The largest uptake of thyroid glands was(102.74±9.39)%ID/g at 2h after injection. The uptake of tumors was(0.026±0.003)%ID/g at 24h after injection. The difference of %ID/g was not significant (P=0.27) in tumors and kidneys at 24h after injection.④The difference of %ID/g was significant (P<0.01) in tumors and kidneys between 188Re-IGF-1A group and 188ReO4- group. The largest ratio of tumors in the two groups was 74.10 at 24h after injection.⑤A fter being injected, 188Re-IGF-1A formed clear images in tumors. 5d later, nothing but tumors can be seen .Conclusions: 188Re -IGF-1A has good affinity with human pancreatic cancer , and the tumor to muscle ratios in nude mice is high. So 188Re-IGF-1A is expected to be used for targeting therapy of human pancreatic carcinoma. We can also observe its biodistribution in vitro.
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