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Objective To investigate the effects of intratumoral implantation of ~(32)P-CP-PLLA seeds on the normal canine liver tissue and to exolore the metabolism of ~(32)P-CP-PLLA seeds implanted in the liver of experimental dogs.Methods Twelve beagles were enrolled in this study.The dogs were randomly and equally divided into four groups:group A(185 MBq),group B(370 MBq),group C(740 MBq)and group D(0 MBq).By using laparotomy procedure ~(32)P-CP-PLLA seeds were implanted into dog's liver.CT scan was performed before operation as well as before the dog was sacrificed.All dogs were sacrificed three months after the implantation.Before the procedure and 1,2,4,8 and 12 weeks after the procedure the blood tests and serum biochemical tests were conducted.One dog from group B and group C was selected respectively and was fed in a metabolic cage.Within one month after the procedure the cpm in feces and in urine was determined every 24 hours.One dog was picked out from each of the three groups and was punctured to get its liver tissue for pathologic exam each time at 1,2,4,8 and 12 weeks after the implantation,and SPECT imaging was also performed at the same time.Pathologic study,both macroscopic and microscopic(including optical and electronic microscopy)was made to observe the liver damage after the dog was sacrificed.The statistical analysis was processed by using SPSS 13.0 software and the measuring data were expressed with mean±standard deviation((x)±s).Results Two months after the procedure,serological examination found that the serum alkaline phosphatase(BKP)in both group Band group C was significantly higher than that in other groups,the difference was statistically significant (P ＜0.05),and the BKP levels returned to normal in three months.The postoperative 30-day inspection of the urine showed that the radioactive particles slowly released into the body and eliminated from the body with the urine and feces,mainly through the renal excretion.The 30-day cumulative percentage of eliminated radioactive dose in the urine and in the feces was 6.34% and 11.64% respectively.No sign of particle displacement was found on SPECT imaging.On autopsy three months after the implantation,the size of the radioactive seeds became smaller and fragile.With the radioactive dose used increasing,the area of liver damage at the site of seed implantation became bigger,which was demonstrated on CT scan,macroscopic exam and pathologic study.The local damaged focus of the liver caused by ~(32)P-CP-PLLA seeds was manifested as a spherical lesion which was encysted by a layer of fibrous tissue with an edematous zone peripherally.Conclusion The implantation of ~(32)P-CP-PLLA seeds in dog's liver causes only localized hepatic damage with no general adverse effects.The implanted seeds can slowly release the radioactive dose and will not immigrate to other organs in the body.Besides,the seeds possess excellent stability,targeted orientation and safety.
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Objective To explore the toxicity and safety of 32P-CP-PLLA seeds interstitial implantation. Methods 30 beagle dogs were randomly divided into 10 groups according to different drugs (32P-CP-PLLA and 32P-CP),different doses (185, 370 and 740 MBq) and different sites (gluteus and liver). At different time-points after surgery, the weights of dogs were measured. The blood routine and blood biochemical indexes,PC Ⅲ ,HA,CG,PCⅣ and LN were examined. ECT imaging was performed and histology was observed dynamically. Blood, urine and faeces were measured continuously for 12 weeks and 30 days, respectively. Results ECT imaging demonstrated in seed groups and 32P-CP muscle groups radioactivity concentrated continuously in the area of implantation, without liver imaging. 471.67 MBq/m2 of 32 P-CP was injected in liver,while the absorbed dose was 31 Gy,without significant liver damage. When the dose was 794. 28 MBq/m2 , the absorbed dose was 56 Gy,with strong liver and systemic toxicity. But implanting seeds at the same or higher dose, the absorbed dose was 89.83-178.68 Gy in the area of implantation, and the rest liver was 1.09-2. 18 Gy,without liver damage. Dogs in liver group died at 23, 29 and 45 d, respectively, and the inspections of liver fibrosis were higher than the means of the other groups.Blood routine and blood biochemistry indexes between the other groups showed no significant differences.Effective half-life of 32P-CP-PLLA was 11.78 d, while that of 32P-CP was 6. 82 d in liver, and 8. 73 d in gluteus. Mild to moderate injury were found in liver group at 4 weeks. Moderate to serious injury were found. Liver cell necrosis and proliferation were found at 4-6 weeks in other liver groups. In muscle groups,only cellular edema was found in muscle groups at 2 week. The radioactivity count rate in blood for seed groups showed slowly jagged decreasing over time, and decreased exponentially for 32PCP groups. The radioactivity count rate in urine and faeces were multi-peak descending in seed groups. Conclusions 32P-CP-PLLA seeds have the advantages of suitable target location, degradable, non-migration and easy to protection, and it could be used in treatment for different blood supply types of solid tumors. Liver of beagle dog could endure the dose from 32 P-CP-PLLA seed twice as 32P-CP lethal dose.
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Objective To explore the possibility and safety of ~(32)P-colloidal chromic phosphate interstitial injection.Methods Ten Beagle dogs were randomly divided into 5 groups (n ＝ 2) according to different doses (185 and 370 MBq) ,different sites (gluteus maximus and liver) and cold colloid as a control group.At different time-points after surgery,the weights of dogs were measured,and the blood and blood biochemical inspections were examined.ECT imaging was performed and histomorphology was observed dynamically.The radioactive counts of body surface for 90 days,blood for 12 weeks and urine and feces for 30 days were measured continuously.Measured data were expressed by mean ±standard error ((x) ±s) and SPSS 13.0 software was used for statistical analysis.Results ECT imaging demonstrated that the whole liver imaging was obtained although the radioactive distribution was uneven in liver groups,and the radioactivity concentrated continuously in the area of injection,but no liver imaging in muscle groups.Dogs in group 4 lost weight progressively and reduced by 2.7 kg till 45 d after operation.While the mean weight increments in the other groups were 3.0,1.6,0.8 and 3.1 kg in order.In group 4,PLT and RBC reduced obviously.Dogs died at 23 or 45 d.AST and ALT were elevated sharply before death.In the other groups,blood and blood biochemistry inspection showed there were no significant statistical differences.The highest radioactive counts after operation were obtained from the injection spot,while the urinary bladder and the spleen were followed.The peak of blood cpm in liver groups presented at 5 min.Peak values were 0.5 × 10~7/min and 1.0 × 10~7/min,respectively.The blood cpm in the muscle groups was always maintained at 3 × l0~5/min.Histology study showed the hyperemia dropsy changes in muscle groups and 185 MBq liver group in 4 weeks,while after 8 weeks the organizational structure restored normally.There were partial liver cells necrosis in 4 weeks,and the massive liver cells balloon type changes in 6 weeks,as well as obvious hyperemia dropsy and the hepatic lobe structure unclear in 370 MBq liver group.For the radioactive counts of urine and excrement,the peak appeared at 13 and 12 d respectively,and the peak values were (42.0 ±3.3) × 10~4 and (29.6 ±4.5) ×10~4 /min in muscle groups,respectively ;while the peak appeared at 5 and 9 d,respectively and the peak values were (49.0 ± 10.2) × 10~4 and (28.5 ± 7.1) × 10~4 /min in liver groups,respectively.Cumulative excretion ratios in urine and excrement were 36.58% and 10.62% in muscle groups,respectively and 23.48% and 8.76% in liver groups till 30 d,respectively.The liver absorbed doses were 30.6 and 55.6 Gy in liver groups,while those were 2.3 and 6.5 Gy in muscle groups.The maximus absorbed doses of gluteus were 53.4 and 98.1 Gy in muscle groups.Conclusions When ~(32)P- colloidal chromic phosphate of 794.39 MBq/m~2 was injected into the liver of Beagle,the liver absorbed dose was 56 Gy,which could be lethal dose for its strong liver toxicity and systemic side effects.Injection of 463.98-772.93 MBq/m~2 in muscle of Beagle could be safe.~(32) P-colloidal chromic phosphate interstitial injection is secure to treat the solid tumors with poor and middle blood supply which could be reached by puncture.
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Twenty six uncontrolled patients with Graves′ disease were treated with thyroid artery embolism. Twenty two cases were followed for 24 60 months. The long term effect was observed after thyroid artery embolism. The results showed that the long term cure rate is 81.4% (18/22).