核医学课件：分子核医学

1、分子核医学的主要研究内容代谢显像: 葡萄糖，核苷酸，氨基酸，乏氧代谢受体显像基因显像: 酶，受体，转运体报告基因放射免疫显像凋亡显像报告基因显像 基因治疗和干细胞移植治疗将是治疗某些疾病具有发展前景的方法如何监测携带治疗基因的病毒是否成功到达靶器官并有效表达，是基因治疗的关键在重组治疗基因的病毒DNA上同时插入一段报告基因，治疗基因与报告基因共表达，只要在活体内探测到报告基因的出现，就能间接反映治疗基因的表达，就能够在活体内无创伤性检测治疗基因的成功表达，以及表达的部位、持续时间、表达的量等报告基因系统酶/底物报告基因系统：报告基因表达产物为一种具有生物活性的酶，酶与相应底物作用生成的代谢产物

2、在报告基因表达的细胞内浓聚，借助底物上携带的放射性核素进行成像，如HSV-tk等受体/配体报告基因系统：报告基因表达的蛋白质是一种细胞表面受体，与核素标记的特异性配体结合，显像转运蛋白/底物报告系统：钠/碘转运体NIS，去甲肾上腺素转运蛋白NIS是一种膜蛋白，含13个跨膜的结构域，一个细胞外氨基末端和一个细胞内羧基末端；NIS蛋白有3个可能的N-糖基化位点；1个位于细胞外第四环，2个位于细胞外最后一环NIS钠/碘转运体碘的主动转运是通过甲状腺细胞膜上的钠碘同向转运体(NIS)介导的，协同转运2个Na+和1个I，其能量由跨膜的Na+ 梯度提供。I通过顶膜的离子通道进入滤泡腔内，在此经过甲状腺过氧

3、化物酶(TPO)的氧化催化，进行甲状腺激素合成NIS钠/碘转运体分子显像无创监测MLC-2v为启动子的双基因重组腺病毒靶向治疗心肌缺血的实验研究国家自然科学基金NSFC(30900375)Human NIS gene for tumor radionuclide therapy and report gene imagingRetinoic acid and tributyrin restore hNIS gene expression and radioiodine uptake in a poorly differentiated follicular thyroid carcinoma.

4、Baculovirus-mediated transfer of hNIS gene into tumor cell for radionuclide therapy and imaging.A novel positive feedback effect of 131I-promoted Bac-Egr1-hNIS expression in malignant glioma via baculovirus.Baculovirus-mediated transfer of hNIS gene as an ideal radionuclide reporter gene imaging for

5、 monitoring the fate of human stem cells. All-trans retinoic acid (ATRA) or/and tributyrin (TB) induces radioiodine uptake in FTC-133 cells. Inhibitory effect of all-trans retinoic acid (ATRA) or/and tributyrin (TB) on the proliferation of FTC-133 cellsRetinoic acid and tributyrin restore hNIS gene

6、expression Preclinical tumor therapy research. Tumor control rate: 41.2% Promising strategy for clinical tumor gene therapy.Bac-hNIS infected tumor cells were selectively killed by exposure to 131I and accumulated more 131I than that of the control monitored.Baculovirus-mediated transfer of hNIS gen

7、eDose-response transfect efficiency of 131I-stimulated hNIS expression with Bac-Egr1-hNIS. hNISEgr1hNIShNISnucleus cytoplasm hNIShNIS131I,188Re131I,188Re131I,188ReTherapy model of positive feedback. As Egr1 promoter is activated by 131I and may promote hNIS expression, hNIS also induces 131I uptake

8、and activates Egr1.A novel positive feedback effect of 131I-promoted Bac-Egr1-hNIS The use of MOI= 800 in hUCB-MSCs yielded the highest GFP+ %. GFP expression of infected hUCB-MSCs was especially stable in the first 4 days and remained at a high level for at least 1 week after infection.hNIS reporte

9、r gene imaging1, Bac-NIS-infected hUCB-MSCs; 2, mock-infected hUCB-MSCs; 3, thyroid; 4, heart; 5, stomach; 6, intestinal area; 7, bladder. After administration with Na125I, the right axilla of mice, where was transplanted with Bac-NIS-infected hUCB-MSCs 24 h before, was obviously visible by SPECT im

10、aging.hNIS reporter gene imagingHuman plasminogen kringle 5 for anti-angiogenesis therapyPreparing and radionuclide labelled recombinant human plasminogen kringle5 (rhk5)Baculovirus Mediated Experimental Research on Targeted Egr1-Kringle 5 Gene Radiotherapy in Lung AdenocarcinomaBaculovirus Vector-M

11、ediated Transfer of Sodium Iodide Symporter and Plasminogen Kringle 5 Genes for Tumor Radioiodide Therapyan internal proteolytic fragment of plasminogen, is an inhibitor of angiogenesis. low molecular weight, low immunogenicity, high affinity and biological activity.rhk5 protein was expressed and pu

12、rified. The purified protein has biological activity.rhK5SDSMTTSDSWestern Blotrhk5 protein17kD25kD10kD34kD34kD25kD17kD10kDHuman plasminogen kringle 5 (rhk5)99mTc-rhk5131I-rhk5188Re-rhk5 0.5h 2 h 4 hrhk5 was labeled with radionuclides, 99mTc, 131I and 188Re131I-rhk5 can inhibit effectively tumor grow

13、th, with a ratio of 34.14%.Early evaluation of anti-tumor therapy with 188Re-rhk5 by 18F-FDG micro PET/CT.Radionuclide labelled rhk5 before after before after control group treatment groupEvaluation of anti-tumor therapy with 188Re-rhk5by Micro PET/CT Scheme of Radio-inducible K5 gene expression. As

14、 Egr1 promoter is activated by 131I and may promote K5 expression.The apoptotic percentage Bac-Egr1-K5 transfected HUVECs increased in relation to the irradiation dose.Baculovirus-mediated transfer of Egr1 promoter-K5 gene into HUVECsSPECT images at 0.5 h post-injection with Na131I showed that the t

15、umor was clearly visualized in the baculovirus-infected groups.Bac-hTERT-NIS-Egr1-K5-infected tumors showed a significant growth retardation compared to control groups or the other two treated groups after 37 MBq 131I treatment Baculovirus Vector-Mediated Transfer of Sodium Iodide Symporter and Plas

16、minogen Kringle 5 Genes K5 staining was increased in the Bac-hTERT-NIS-Egr1-K5 + 131I group.Treatment with Bac-hTERT-0-Egr1-K5 + 131I reduced the number of tumor microvessels compared to the control groups Baculovirus Vector-Mediated Transfer of Sodium Iodide Symporter and Plasminogen Kringle 5 Gene

17、s磁 共 振磁共振分子成像方法波谱分析及成像(MRS, MR spectrum)脑功能成像(BOLD-fMRI, blood oxygen level depended)弥散加权成像（DWI, diffusion weighted imaging)灌注成像（PWI, perfusion weighted imaging)基因治疗与显像：氧化铁纳米颗粒，转铁蛋白受体细胞调亡显像：金属造影剂标记 annexin-V正常颅脑波谱Cho在3.2ppm胆碱峰Cholip恶性肿瘤MRS 波谱成像Cho乳腺浸润性导管癌肿瘤内磷酸胆碱和甘油磷酸胆碱可在1H MRS中检测到手 指运动区脑功能成像(BOLD-fM

18、RI)DWI早期诊断急性脑梗塞FLAIRDWI陈旧区细胞毒性水肿区灌注成像（PWI）病变明显强化，灌注曲线为平台型光学成像光学成像 (荧光) 的原理 (Choy et al., Mol Imaging 2003; 2:303)小鼠胶质母细胞瘤模型的MRI与光学成像（BLI）MRI光学显像(courtesy: Brian Ross, U Michigan)将转染 Gli-trireporter (B)的U87细胞注入裸鼠的左、右肩. 生成的肿瘤用 Xenogen IVIS 200 光学影像系统观察. 左侧裸鼠注入的是纯 U87细胞，右裸鼠注入的是U87-Gli-tri 细胞. 实验性脑肿瘤 hedgehog 信号途径的生物光学成像（bli）Kpn INot INhe IKpn IA(Zhang et al., Soc. Mol. Im. 2004) bIi fluornuclear荧光图像上面观下面观36,000 ADUs/sec/pix4,900 ADUs/sec/pix(courtesy: Mark Williams, UVA)漫射光学断层扫描 Lewis 肺癌中组织蛋白酶激活的Cy5.5 dye 活体图像(Klose et al., Mol Imaging 2004; 3:230)抗血管生成治疗的超声影像(courtesy: