Shao Guoqiang,Yang Rui,Liang Kai,Yao Xiaochen,Cui Can,Wang Feng,Wang Zizheng.Study on 99Tcm-3P4-RGD2 microSPECT/CT imaging to anti-angiogensis therapeutic effect[J].Chinese Journal of Radiological Medicine and Protection,2017,37(1):12-18
Study on 99Tcm-3P4-RGD2 microSPECT/CT imaging to anti-angiogensis therapeutic effect
Received:June 08, 2015  
DOI:10.3760/cma.j.issn.0254-5098.2017.01.003
KeyWords:MicroSPECT/CT imaging  Quantitive analysis  Integrin αvβ3  Anti-angiogensis therapy
FundProject:国家自然科学基金(81301247);江苏省自然科学基金(BK20130082)
Author NameAffiliationE-mail
Shao Guoqiang Department of Nuclear Medicine, Nanjing Medical University, Nanjing 210006, China  
Yang Rui Department of Nuclear Medicine, Nanjing Medical University, Nanjing 210006, China  
Liang Kai Department of Urology, Affiliated Nanjing Hospital, Nanjing Medical University, Nanjing 210006, China  
Yao Xiaochen Department of Nuclear Medicine, Nanjing Medical University, Nanjing 210006, China  
Cui Can Department of Nuclear Medicine, Nanjing Medical University, Nanjing 210006, China  
Wang Feng Department of Nuclear Medicine, Nanjing Medical University, Nanjing 210006, China  
Wang Zizheng 1. Department of Nuclear Medicine, Nanjing Medical University, Nanjing 210006, China 13770920210@163.com 
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Abstract::
      Objective To investigate the value of integrin αvβ3 targeted microSPECT/CT imaging with 99Tcm-3P4-RGD2 as a radiotracer in tumor anti-angiogenesis therapy.Methods Animal models bearing glioma and prostate cancer xenografts were established by subcutaneously injecting tumor cells U87MG and PC-3 in nude mice. Anti-angiogensis therapy with Avastin was administered via intraperitoneal injection when the tumor diameter reached 6 to 7 mm while saline was served as control group. MicroSPECT/CT imaging was performed with 99Tcm-3P4-RGD2 as radiotracer one day before and 3, 5, 10, 15 days after Avastin administration. Tumor volume and tumor uptake of 99Tcm-3P4-RGD2, expressed as percentage of injected dose (%ID) or%ID per gram (%ID/g) were measured and calculated based on microSPECT/CT. Mice basic condition was monitored and tumor xenograft was harvested in one tumor bearing nude mouse after its sacrifice at each imaging time point. Results Tumor volume of U87MG glioma in the administration group was significantly smaller than that of non-administration control group at 10 d after Avastin adminstration (t=5.81, P<0.05), while no significance was observed between the administration group and its control group of PC-3 tumor (P>0.05). The uptake of 99Tcm-3P4-RGD2 (%ID/g) in U87MG group was higher than that in PC-3 group before Avastin administration (t=10.48, P<0.05), and it decreased to a value less than control (t=3.26, P<0.05) at 3 d after Avastin administration and continually reduced at longer time after administration. PC-3 tumor had less uptake of 99Tcm-3P4-RGD2 in both Avastin administration group and its control group. The pathologic results revealed on that the decrease of tumor integrin β3 expression in U87MG treatment group was mainly on the endothelial cells of the neovessel. Linear relationship was verified between tumor uptake (%ID/g) and integrin β3 expression (y=0.499 1x-0.243 8, R2=0.811 7). Conclusions Complete inhibition of integrin is demonstrated early after Avastin administration. 99Tcm-3P4-RGD2 microSPECT/CT imaging, assessing the expression level of integrin αvβ3 level by quantification of tumor uptake of 99Tcm-3P4-RGD2, is probably an important method to reflect the early therapeutic effect of tumor anti-angiogensis.
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