| NIE Qi,LIU Lu,HUANG Pei-lin,TAN Zhong-bao,WU Qing-hua,GAO Hai-lin,YANG Ze-xuan,HUANG Ying.Long-term toxicity studies on 32P-chromic phosphate-poly-L lactic acid seeds interstitial delivery of beagle dogs[J].Chinese Journal of Radiological Medicine and Protection,2010,30(4):379-386 |
| Long-term toxicity studies on 32P-chromic phosphate-poly-L lactic acid seeds interstitial delivery of beagle dogs |
| Received:March 16, 2010 |
| DOI：10.3760/cma.j.issn.0254-5098.2010.04.002 |
| KeyWords:32P-CP-PLLA seed Interstitial Animal Security |
| FundProject:国家863项目(2007AA02Z471) |
| Author Name | Affiliation | | NIE Qi | Nuclear Medicine Institute of Southeast University Clinic Medicine, Nanjing 210009, China | | LIU Lu | Nuclear Medicine Institute of Southeast University Clinic Medicine, Nanjing 210009, China | | HUANG Pei-lin | Nuclear Medicine Institute of Southeast University Clinic Medicine, Nanjing 210009, China | | TAN Zhong-bao | Nuclear Medicine Institute of Southeast University Clinic Medicine, Nanjing 210009, China | | WU Qing-hua | Nuclear Medicine Institute of Southeast University Clinic Medicine, Nanjing 210009, China | | GAO Hai-lin | Nuclear Medicine Institute of Southeast University Clinic Medicine, Nanjing 210009, China | | YANG Ze-xuan | Nuclear Medicine Institute of Southeast University Clinic Medicine, Nanjing 210009, China | | HUANG Ying | Nuclear Medicine Institute of Southeast University Clinic Medicine, Nanjing 210009, China |
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| Abstract:: |
| 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,PCⅢ,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 32P-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 32P-CP 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 32P-CP-PLLA seed twice as 32P-CP lethal dose. |
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