分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Liu, Renfa
Dai, Zhifei
Shi, Jiyun
Fan, Di
Wang, Fan
Shi, Jiyun
Wang, Fan
Li, Yaqian
Tian, Jie
Jing, Lijia
摘要： This Article reported the fabrication of a robust theranostic cerasome encapsulating indocyanine green (ICG) by incorporating 1,2-distearoyl-sn-glycero-3-phosphoethanol-amine-N-[carboxy(polyethylene glycol)2000]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid monoamide (DSPE-PEG(2000)-DOTA), followed by chelating radioisotope of Lu-177. Its applications in optical and nuclear imaging of tumor uptake and biodistribution, as well as photothermal killing of cancer cells, were investigated. It was found that the obtained cerasome could act efficiently as fluorescence contrast agent as well as nuclear imaging tracer. Encapsulating ICG into cerasome could protect ICG from degradation, aggregation, and fast elimination from body, resulting in remarkable improvement in near-infrared fluorescence imaging, photothermal stability, and in vivo pharmacokinetic profile. Both fluorescence and nuclear imaging showed that such agent could selectively accumulate in tumor site after intravenous injection of the cerasome agent into Lewis lung carcinoma tumor bearing mice, resulting in efficient photothermal ablation of tumor through a one-time NIR laser irradiation at the best time window. The ability to track the uptake of cerasomes on a whole body basis could provide researchers with an excellent tool for developing cerasome-based drug delivery agents, especially the strategy of labeling cerasomes with theranostic radionuclide Lu-177, enabling the ability of the Lu-177-labeled cerasomes for radionuclide cancer therapy and even the combined therapy.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-11
Ma, Teng
Liu, Hao
Sun, Xianlei
Gao, Liquan
Shi, Jiyun
Zhao, Huiyun
Jia, Bing
Wan, Fan
Liu, Zhaofei
Ma, Teng
Liu, Hao
Sun, Xianlei
Gao, Liquan
Jia, Bing
Wan, Fan
Liu, Zhaofei
Shi, Jiyun
Zhao, Huiyun
摘要： Cetuximab is an antiepidermal growth factor receptor (EGFR) monoclonal antibody that has received the approval of the Food and Drug Administration (FDA) for cancer treatment. However, most clinical studies indicate that cetuximab can only elicit positive effects on a subset of cancer patients. In this study, we investigated whether near-infrared fluorescence (NIRF) imaging of tumor vascular endothelial growth factor (VEGF) expression could be a biomarker for tumor early response to cetuximab therapy in preclinical wild-type and mutant tumor models of the KRAS gene. The treatment efficacy of cetuximab was determined in both HT-29 (wild-type KRAS) and HTC-116 (mutant KRAS) human colon cancer models. A VEGF-specific optical imaging probe (Dye755-Ran) was synthesized by conjugating ranibizumab (an anti-VEGF antibody Fab fragment) with a NIRF dye. Serial optical scans with Dye755-Ran were performed in HT-29 and HTC-116 xenograft models. By using longitudinal NIRF imaging, we were able to detect early tumor response on day 3 and day 5 after initiation of cetuximab treatment in the cetuximab-responsive HT-29 tumor model. Enzyme-linked immunosorbent assay (ELISA) confirmed that cetuximab treatment inhibited human VEGF expression in the KRAS wild-type HT-29 tumor but not in the KRAS mutant HCT-116 tumor. We have demonstrated that the antitumor effect of cetuximab can be noninvasively monitored by serial fluorescence imaging using Dye755-Ran. VEGF expression detected by optical imaging could serve as a sensitive biomarker for tumor early response to drugs that directly or indirectly act on VEGF.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-05
Dong, Chengyan
Yang, Sujuan
Zhao, Huiyun
Liu, Zhaofei
Jia, Bing
Wang, Fan
Dong, Chengyan
Yang, Sujuan
Zhao, Huiyun
Liu, Zhaofei
Jia, Bing
Wang, Fan
Dong, Chengyan
Shi, Jiyun
Wang, Fan
Zhao, Huiyun
Zhong, Lijun
Wang, Fan
摘要： We describe herein dual-modality imaging of intraperitoneal colon tumor using an avidin/biotin pretargeting system. A novel dual-modality probe,Tc-99m-HYNIC-lys(Cy5.5)-PEG4-biotin,was designed, synthesized and characterized. Single-photon emission computed tomography/computed tomography (SPECT/CT) imaging and near infrared fluorescence (NIRF) imaging were developed using intraperitoneal LS180 human colon adenocarcinoma xenografts. Following avidin preinjection for 4 hours, 99mTc-HYNIC-lys(Cy5.5)-PEG4-biotin could successfully detect colon tumors of different sizes inside the abdominal region using both modalities, and the imaging results showed no differences. Biodistribution studies demonstrated that the tumors had a very high uptake of the probe (TcHYNIC)-Tc-99m-lys(Cy5.5)-PEG4-biotin(12.74 +/- 1.89% ID/g at 2 h p.i.), and the clearance from blood and other normal tissues occured very fast. The low tumor uptake in the non-pretargeted mice (1.63 +/- 0.50% ID/g at 2 h p.i.) and tumor cell staining results showed excellent tumor binding specificity of the pretargeting system. The ability of the novel probe to show excellent imaging quality with high tumor-to-background contrast, a high degree of binding specificity with tumors and excellent in vivo biodistribution pharmacokinetics should prove that the avidin/biotin based dual-modality pretargeting probe is a promising imaging tool during the entire period of tumor diagnosis and treatment.
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