ABSTRACT
Objective To investigate the value of integrin αvβ3 targeted microSPECT/CT imaging with 99 Tcm-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 99 Tcm-3P4-RGD2 as radiotracer one day before and 3, 5, 10, 15 days after Avastin administration .Tumor volume and tumor uptake of 99 Tcm-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, P0.05).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 99 Tcm-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 .99 Tcm-3P4-RGD2 microSPECT/CT imaging, assessing the expression level of integrin αvβ3 level by quantification of tumor uptake of 99 Tcm-3P4-RGD2 , is probably an important method to reflect the early therapeutic effect of tumor anti -angiogensis .
ABSTRACT
Objective To investigate the value of single photon emission computed tomography (CT) imaging and transmis‐sion CT imaging (microSPECT‐CT ) bremsstrahlung imaging for the solid tumor mesenchymal implantaion of 32 P‐chromic phos‐phate‐paclitaxel‐poly‐L‐lactic acid (32 P‐CP‐PSP‐PLLA) sustained release seeds and to investigate the 32 P in vivo biodistribution and degradation sustained release churacteristics .Methods The animal model of prostate cancer subcutaneously transplanted tumor was established .32 P‐CP‐PSP‐PLLA sustained‐release seeds were intratumorally implanted by the mediation of microSPECT‐CT brems‐strahlung imaging and the 32 P distribution in bearing tumor mouse was verified by the imaging and biological distrubtion tests .The ultrastructural changes of 32 P seeds were observed by the scanning electron microscope .Results The MicroSPECT/CT brems‐strahlung imaging could effectively guide the intratumoral implantation operation of the 32 P sustained‐release seeds with clear visu‐alization .Partial sustained‐release 32 P was remained in the tumor tissues with little distribution in important organs of spleen and liver ,which was proved by the biodistribution results .The particle surface and inside micropores and tunnels formation ,their pro‐gressive increase ,fusion and connection were found by the electronic microscope after the 32 P sustained‐release seeds intratumoral implantation .Conclusion The MicroSPECT/CT bremsstrahlung imaging can effectively monitor the 32 P sustained‐release seeds and their in vivo biodistribution and lays a foundation for the sustained‐release seeds prostatic targeted implantation .
ABSTRACT
Objective To evaluate the anatomic localization and size of acute necrotic myocardium in the ischemic-reperfused rat hearts using 99m TC-Glucarate and microSPECT/CT.Methods The ischemic-reperfused ( IR) rat heart models were established by ligating left anterior descending coronary artery for 60 min.99mTC-Glucarate was intravenously injected into the rats 24 hours after IR operations .Images were acquired 30 min after administration of 99m TC-Glucarate using microSPECT/CT. Anatomic localization and size of acute necrotic myocardium were analyzed with microSPECT/CT imaging , and these results were compared to those determined by triphenyltetrazolium chloride ( TTC ) staining.Results The microSPECT/CT images showed hot spot accumulations of 99mTC-Glucarate in IR hearts (the heart-to-liver ratio was 1.90 ±0.33), not in controls (P <0.05).The anatomic localization of 99mTC-Glucarate-labeled necrotic myocardium were in correspondence with TTC staining results .The hot spot size was related significantly to necrotic myocardial size determined by TTC staining ( R2 =0.964 ) .Conclusions The localization and size of acute necrotic myocardium can be assessed by non-invasive microSPECT/CT imaging with99m Tc-Glucarate.
ABSTRACT
The process of drug discovery and development requires substantial resources and time. The drug industry has tried to reduce costs by conducting appropriate animal studies together with molecular biological and genetic analyses. Basic science research has been limited to in vitro studies of cellular processes and ex vivo tissue examination using suitable animal models of disease. However, in the past two decades new technologies have been developed that permit the imaging of live animals using radiotracer emission, X-rays, magnetic resonance signals, fluorescence, and bioluminescence. The main objective of this review is to provide an overview of small animal molecular imaging, with a focus on nuclear imaging (single photon emission computed tomography and positron emission tomography). These technologies permit visualization of toxicodynamics as well as toxicity to specific organs by directly monitoring drug accumulation and assessing physiological and/or molecular alterations. Nuclear imaging technology has great potential for improving the efficiency of the drug development process.