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1. 发明申请

WO2009140743A3 BLOOD IMAGING 审中-公开
标题翻译：血液成像
公开(公告)号：WO2009140743A3
公开(公告)日：2010-06-24
申请号：PCT/BE2009000027
申请日：2009-05-25
申请人： UNIV LEUVEN KATH , BORMANS GUY , VERBRUGGEN ALFONS
发明人： BORMANS GUY , VERBRUGGEN ALFONS
IPC分类号： A61K51/04 , C07C311/37 , C07F1/08 , C07F5/00 , C07F13/00
CPC分类号： A61K51/04 , A61K51/0478 , C07B59/001 , C07B2200/05 , C07C311/29 , C07C311/46 , C07F13/005
摘要： The invention generally relates to the application of imaging techniques, in particular positron emission tomography (PET) or single photon emission tomography (SPECT), in the assessment of physiological parameters in a subject. The compounds of the present invention were shown to be cell membrane permeant and to have a specific binding affinity (or substrate affinity) for the carbonic anhydrases type I and II, and are accordingly useful for the in vivo and in vitro labeling of erythrocytes (RBC). It is accordingly an object of the present invention to provide said novel compounds, in particular the radio labeled variants thereof, and their use in imaging techniques to perform the assessment of physiological parameters, such as blood volume measurements, or blood flow measurements.
摘要翻译：本发明通常涉及成像技术，特别是正电子发射断层摄影（PET）或单光子发射断层摄影（SPECT）在评估受试者生理参数方面的应用。本发明的化合物被证明是细胞膜透膜，并且对于I型和II型碳酸酐酶具有特异性结合亲和力（或底物亲和力），因此可用于红细胞（RBC）的体内和体外标记）。因此，本发明的目的是提供所述新型化合物，特别是其放射性标记的变体，以及它们在成像技术中用于进行诸如血容量测量或血液流量测量的生理参数评估的用途。

2. 发明申请

WO2009067767A3 TARGETED RADIOTHERAPY 审中-公开
标题翻译：目标放射治疗
公开(公告)号：WO2009067767A3
公开(公告)日：2010-01-21
申请号：PCT/BE2008000099
申请日：2008-11-26
申请人： UNIV LEUVEN KATH , NI YICHENG , VAN DE PUTTE MARIE , DE WITTE PETER , VERBRUGGEN ALFONS , MARCHAL GUY
发明人： NI YICHENG , VAN DE PUTTE MARIE , DE WITTE PETER , VERBRUGGEN ALFONS , MARCHAL GUY
IPC分类号： A61K51/04 , A61P35/00
CPC分类号： A61K51/04
摘要： The present invention concerns a therapeutically labeled napthodianthrone or phenanthro[1,10,9,8-opqra]perylene-7,14-dione compound, which comprises a chemical element or an isotope that has an unstable nucleus and emits radiation during its decay to a stable form sufficient to destroy neighboring cells or tissues for use in a targeted radiotherapy to enhance curability of a warm-blooded animal that has been subjected to a necrosis-inducing antitumor therapy. A particular advantage of present invention is that viable rim resistant to a necrosis-inducing antitumor therapy such as vascular targeting agent (VTA) can be supplemented by one single or repeated doses of a therapeutically radiolabeled small molecule necrosis-avid chemical compound treatment to enhance the curability. Examples of necrosis inducing therapies are for instance minimally invasive tumor ablations applied chemically by percutaneous injection of ethanol or acetic acid, or physically by cryotherapy, microwave, focused ultrasound, interstitial laser therapy and radio- frequency ablation (RFA); by chemotherapies using cytotoxic agents or vascular targeting agents (VTA); and by external or internal radiotherapies.
摘要翻译：本发明涉及一种治疗上标记的阴蒂龙酮或菲咯啉[1,10,9,8-吖庚因]二萘嵌苯-7,14-二酮化合物，其包含具有不稳定核的化学元素或同位素，并在其衰变期间发射辐射足以破坏用于靶向放射治疗的相邻细胞或组织的稳定形式，以增强已经进行坏死诱导的抗肿瘤治疗的温血动物的固化性。本发明的一个特别优点是可以通过一种单独或重复剂量的治疗性放射性标记的小分子坏死化学化合物治疗来补充对坏死诱导的抗肿瘤治疗如血管靶向剂（VTA）有抗性的活性边缘，以增强固化性。坏死诱导疗法的实例是例如通过经皮注射乙醇或乙酸而化学施用的微创肿瘤消融，或通过冷冻治疗，微波，聚焦超声，间质激光治疗和射频消融（RFA）物理化的微创肿瘤消融。通过使用细胞毒剂或血管靶向剂（VTA）的化疗; 以及外部或内部放射治疗。

3. 发明申请

WO2010105315A3 REPORTER GENE CONSTRUCTS FOR PET 审中-公开
标题翻译：报告基因构建PET
公开(公告)号：WO2010105315A3
公开(公告)日：2010-11-18
申请号：PCT/BE2010000022
申请日：2010-03-22
申请人： KATHOLIEKE UNIVERSIFEIT LEUVEN , BAEKELANDT VEERLE , BORMANS GUY , DEBYSER ZEGER , DEROOSE CHRISTOPHE , EVENS NELE , TOELEN JAAN , VANDEPUTTE CAROLINE , VAN LAERE KOENRAAD , VERBRUGGEN ALFONS
发明人： BAEKELANDT VEERLE , BORMANS GUY , DEBYSER ZEGER , DEROOSE CHRISTOPHE , EVENS NELE , TOELEN JAAN , VANDEPUTTE CAROLINE , VAN LAERE KOENRAAD , VERBRUGGEN ALFONS
IPC分类号： C07K14/705 , C12Q1/68
CPC分类号： C07K14/70571 , A61K51/0455 , A61K51/0463 , C12Q1/6897
摘要： The present invention relates to the field of in vivo molecular imaging and, more particularly to a method for reporter gene imaging via positron emission tomography (PET), which can be applied in nervous system (brain, cerebrum, cerebellum, medulla, pons, spinal cord, sciatic nerve) and particularly in the brain. The present invention also involves type 2 cannabinoid receptor (CB2) based reporter gene constructs and a reporter probe or tracer (reporter system) for use in a molecular imaging therapy for instance by PET. The reporter gene encodes the reporter protein to which the reporter probe binds.
摘要翻译：本发明涉及体内分子成像领域，更具体地说，涉及通过正电子发射断层摄影（PET）的报告基因成像方法，其可应用于神经系统（脑，大脑，小脑，髓质，脑脊髓，脊髓）绳，坐骨神经），特别是在脑中。本发明还涉及基于2型大麻素受体（CB2）的报告基因构建体和用于例如PET的分子成像治疗的报道探针或示踪剂（报道系统）。报告基因编码报告基因探针结合的报道蛋白。

4. 发明申请

WO2016065435A3 METHODS FOR LOW TEMPERATURE FLUORINE-18 RADIOLABELING OF BIOMOLECULES 审中-公开
标题翻译：低温氟-18生物分子的放射性标记方法
公开(公告)号：WO2016065435A3
公开(公告)日：2016-06-30
申请号：PCT/BE2015000063
申请日：2015-10-29
申请人： UNIV LEUVEN KATH
发明人： MUSTHAKAHMED AHAMED MUNEER SYED , BILLAUD EMILIE , BORMANS GUY , CLEEREN FREDERIK , LECINA JOAN , VERBRUGGEN ALFONS
IPC分类号： C07C229/16 , C07B59/00 , C07K1/13
CPC分类号： C07C229/16 , C07B2200/05 , C07B2200/07 , C07C215/50 , C07C229/14 , C07C229/38 , C07C229/42 , C07C259/06 , C07C331/28 , C07C2601/08 , C07C2601/14 , C07D213/38 , C07D243/08 , C07D255/02
摘要： New chelators such as H3L1, H3L2, H3L3, H3L26 and derivatives were synthesized for the complexation of {Al18F}2+. These new chelators are able to complex {AI18F}2+ with good radiochemical yields using a labeling temperature of 37 °C. The stability of the new Al18F- complexes was tested in phosphate buffered saline (PBS) at pH 7 and in rat serum. AI18F-L3 and AI18F-L26 showed a stability comparable to that of the previously reported Al18F-NODA. Moreover, the biodistribution of Al18F-L3 and AI18F-L26 showed absence of in vivo demetallation since only very limited bone uptake was observed, whereas the major fraction of activity 60 min p.i. was observed in liver and intestine due to hepatobiliary clearance of the radiolabeled ligand. The chelators H3L3 and Al18F-L26 demonstrated to be a good lead candidates for the labeling of heat sensitive biomolecules with 18F-fluorine and derivatives have been synthesized. We have explored the complexation of {AI18F}2+ with new chelators and obtained very favourable radiochemical yields (> 85%) using a labeling temperature of 37 °C. The stability of the new Al18F-complexes was tested in phosphate buffered saline (PBS) at pH 7 and in rat serum at 37 °C, where AI18F-L3 and AI18F-L26 showed a stability comparable to that of the previously reported Al18F-NODA. Moreover, the biodistribution of Al18F-L3 and Al18F-L26 showed high stability, since only very limited bone uptake- which would be an indication of release of fluorine-18 in the form of fluoride- was observed, whereas the major fraction of activity 60 min p.i. was observed in liver and intestines due to hepatobiliary clearance of the radiolabeled ligand. The chelators H3L3 and H3L26 demonstrated to be good lead candidates for the labeling of heat sensitive biomolecules with 18F-fluorine and several derivatives have been synthesized.
摘要翻译：合成了新的螯合剂，如H3L1，H3L2，H3L3，H3L26和衍生物，用于{Al18F} 2+的络合。这些新的螯合剂能够使用37°C的标记温度以良好的放射化学产率复合{AI18F} 2+。在pH 7的磷酸盐缓冲盐水（PBS）和大鼠血清中测试新的Al 18 F-复合物的稳定性。 AI18F-L3和AI18F-L26显示出与先前报道的Al18F-NODA相当的稳定性。此外，Al18F-L3和Al18F-L26的生物分布显示没有体内去金属化，因为仅观察到非常有限的骨吸收，而活性的主要部分为60分钟。在肝脏和肠中由于放射性标记的配体的肝胆清除而被观察到。已经合成了螯合剂H3L3和Al18F-L26，它们是用18 F-氟和衍生物标记热敏生物分子的良好主要候选物。我们研究了{AI18F} 2+与新螯合剂的络合作用，并使用37°C的标记温度获得了非常有利的放射化学产率（> 85％）。在pH 7的磷酸盐缓冲盐水（PBS）中和37℃的大鼠血清中测试新的Al 18 F-复合物的稳定性，其中AI 18 F-L3和Al 18 F-L 26表现出与先前报道的Al 18 F-NODA相当的稳定性。此外，Al 18 F-L 3和Al 18 F-L 26的生物分布显示出高稳定性，因为仅观察到非常有限的骨吸收 - 其可以表明以氟化物形式释放氟-18，但活性的主要部分60 min pi 在肝脏和肠内由于放射性标记的配体的肝胆清除而观察到。已经合成了螯合剂H3L3和H3L26，它们是用18 F-氟和多种衍生物标记热敏生物分子的良好主要候选物。

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