活体动物生物发光成像技术在新药研究中的应用

活体动物体内成像技术为研究人员提供了一个观察实验动物体内生物学现象的窗口，使在分子水平上实时跟踪生物学过程成为可能。这种技术采用了荧光素酶,当整合到细胞、微生物或实验动物上的荧光素酶基因表达时，在有底物荧光素存在的情况下，会产生生物发光。利用高灵敏度相机可观察这些细胞、微生物或目的基因在动物体内各个器官的表达及对药物的反应，从而获取生物体内的基因表达、疾病发展和新药的药理、药效、PD/PK、安全性/毒性和给药方式评价等信息。fficeffice" />

活体动物体内成像技术使在整体动物水平上进行高通量、大规模药物筛选成为可能。这项技术已经被大多数跨国制药公司（如诺华、默克、辉瑞等）和生物技术公司广泛应用于药物的基础研发及临床前试验过程中，应用该技术进行的新药研究已经获得美国FDA的认可。该技术以其高灵敏度、高通量及定量研究的特点，已经为新药研究的模式带来革命性变革！  

 

以下是相关文献，与大家分享！ 

 

1．  Cdk2抑制剂的药物动力学模型

Bioluminescent imaging of Cdk2  inhibition in vivo

       Nature Medicine 10(6), 643-648, Jun  2004

 

2．  喜树碱类抗癌新药托泊替康(topotecan)的临床前研究

Schedule-dependent inhibition of hypoxia-inducible  factor –1α   protein  accumulation ,angiogenesis ,and tumer growth by  topotecan in U251 HRE glioblastoma  xenografts

      Cancer Research 64, 6845-6848, Oct  1, 2004

 

3．  Sugen公司(已经被Pfizer收购)抗乳腺癌药物SU11248的临床前药效评价

In Vivo Antitumer Activity of SU11248，a Novel Tyrosine Kinase Inhibitor Targeting Vascular Endothelial Growth Factor and Platelet-derived Growth Factor Receptors: Determination of a Pharmacokinetic/Pharmacodynamic Relationship

Clinical Cancer Research 9, 327-337, Jan 2003

 

4．  抑制低氧诱导因子通路的小分子药物黑毛霉素（chetomin）抗癌疗效评价

Small molecule blockade  of transcriptional coactivation of the hypoxia-inducible factor  pathway

Cancer  cell  , 6 ,33-43 ,Jul  ,2004

 

5．  酪氨酸激酶抑制剂PKC412治疗急性淋巴细胞白血病的疗效观察

Inbibition of  FLT3 in MLL:Validation of a therapeutic target identified by gene  expression based classification

Cancer  cell  , 3,173-183 ,Feb ,2003  

      

6．  AMD 3100 治疗原发性脑肿瘤的药效评价

A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors.

PNAS 100(23), 13513-13518, Nov 11, 2003

 

7．  Epothilone 类似物治疗骨髓瘤的疗效观察

Investigation of antitumor effects of synthetic epothilone analogs in human myeloma models in vitro and in vivo

PNAS 102(30): 10640-10645 , July 26 ,  2005

 

8．  细胞毒抗癌药物MLN2704（抗体化疗复合物）治疗成骨细胞前列腺癌转移的疗效观察

A Prostate-Specific Membrane Antigen-Targeted Monoclonal Antibody-Chemotherapeutic Conjugate Designed for the Treatment of Prostate Cancer

      Cancer Research 64, 7995-8001, Nov 1, 2004

 

9．  药物代谢

        The orphan nuclear receptor HNF4α determines PXR- and CAR-mediated xenobiotic induction of CYP3A4. 

              Nature Medicine 9(2), 220-224, Feb 2003

 

10．              药物抗药性逆转筛选模型

Imaging reversal of multidrug resistanse in  living  mice with bioluminescence : MDR1 P-glycoprotein transports coelenterazine

PNAS 101(6),1702-1707 ,Feb 10  ,2004

 

11．              药物对蛋白质相互作用的影响

Kinetics of regulated  protein-protein interactions revealed with firefly luciferase complementation imaging in cells and living animals

PNAS 101(33), 12288-12293, Aug 17 , 2004

 

12．              治疗传染性心内膜炎的抗生素筛选模型

Real-time in vivo bioluminescent imaging for evaluating the efficacy of antibiotics in a rat Staphyococcus aureus endocarditis model

Antimicrobial Agent and Chemotherapy 49(1): 380–387，Jan , 2005

 

13．              抗炎症化合物药物筛选模型

An Inducible Nitric Oxide Synthase-Luciferase Reporter System for In Vivo Testing of Anti-inflammatory Compounds in Transgenic Mice.

      The Journal of Immunology, 2003, 170: 6307–631

 

14．              药物毒理评价模型

In vivo bioluminescent monitoring of chemical toxicity using heme oxygenase-luciferase transgenic mice

  Toxicology and Applied Pharmacology    200(3):219-28 ，  Nov 1 ，2004

 

15．              关于药物研究动物模型的一篇综述

Reporter mice and drug discovery and development

Nature Reviews  Drug Discovery Vol. 4, 249-255, March 2005

 

进一步的信息请参见www.xenogen.com  或   www.longmed.com 

 

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