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1. 发明授权

US4778672A Method of isolating radioactive perrhenate or pertechnetate from an aqueous solution 失效
标题翻译：从水溶液中分离放射性高铼酸盐或高锝酸盐的方法
公开(公告)号：US4778672A
公开(公告)日：1988-10-18
申请号：US802779
申请日：1985-11-27
申请人： Edward A. Deutsch , Jean-Luc Vanderheyden
发明人： Edward A. Deutsch , Jean-Luc Vanderheyden
IPC分类号： A61K51/04 , C07B59/00 , G21G4/08 , A61K43/00 , C01G47/00 , C01G57/00
CPC分类号： G21G4/08 , A61K51/04 , C07B59/004 , A61K2123/00
摘要： Pure perihenate is isolated from a aqueous crude solution of perrhenate by first associating the perrherate with a lipophilic counter ion such as tetrabutyl ammonium. This is added to the solution in a form such as tetrabutyl ammonium bromide. Tetrabutyl ammonium perrhenate is formed. The aqueous mixture is then added to a reverse phase separation column such as a C.sub.18 Sep Pak filter which has been previously loaded with the lipophilic counter ion. The aqueous portion of the crude mixture is eluted from the column with water. Subsequently the purified perrhenate associated with the lipophilic counter ion is removed with a less polar solvent such as ethanol. Pertechnetate can also be separated from an aqueous mixture in the same manner. These procedures are particularly suited for isolating relatively pure radioactive forms of perrhenate and pertechnetate such as Re.sup.186 O.sub.4.sup.-, Re.sup.188 O.sub.4.sup.-, and .sup.99m TcO.sub.4.sup.-.
摘要翻译：通过首先将苦参碱与亲脂性抗衡离子如四丁基铵缔合，从硬质酸水溶液的粗水溶液中分离出纯的过氧化钙。将其以诸如四丁基溴化铵的形式加入到溶液中。形成高铼酸四丁基铵。然后将含水混合物加入到反相分离柱如C18 Sep Pak过滤器中，其已经预先装载了亲脂性抗衡离子。粗制混合物的水溶液部分用水从柱中洗脱出来。随后，用极性较小的溶剂如乙醇除去与亲油性抗衡离子缔合的纯化的高铼酸盐。高锝酸盐也可以以相同的方式从含水混合物中分离出来。这些方法特别适用于分离相对纯的放射性形式的高铼酸盐和高锝酸盐，如Re186O4-，Re188O4-和99mTcO4-。

2. 发明授权

US4795626A .sup.99m Tc.sup.(III) myocardial imaging agents which are non-reducable in vivo 失效
标题翻译： 99mTc（III）在体内不可还原的心肌显像剂
公开(公告)号：US4795626A
公开(公告)日：1989-01-03
申请号：US172969
申请日：1988-03-11
申请人： Edward A. Deutsch , Jean-Luc Vanderheyden
发明人： Edward A. Deutsch , Jean-Luc Vanderheyden
IPC分类号： A61K51/04 , C07F13/00 , A61K49/02
CPC分类号： C07F13/005 , A61K51/0476 , A61K2123/00
摘要： A cationic .sup.99m Tc.sup.III myocardial imaging agent is disclosed which has a relatively negative redox potential. This prevents in vivo reduction of the Tc(III) to Tc(II). The redox potential of the Tc(III) is controlled by complexing the Tc with both hard and soft atoms. Preferably four of the atoms complexed to the Tc(III) are hard atoms such as nitrogen or oxygen and the remaining two are soft atoms such as phosphorous or arsenic. These imaging agents are particularly useful in imaging the human heart.
摘要翻译：公开了具有相对负的氧化还原电位的阳离子99mTcIII心肌显像剂。这可以防止Tc（III）体内还原为Tc（II）。 Tc（III）的氧化还原电位通过使Tc与硬原子和软原子相互配合来控制。优选与Tc（III）络合的四个原子是诸如氮或氧的硬质原子，剩下的两个是诸如磷或砷的软原子。这些成像剂在人心脏成像中特别有用。

3. 发明授权

US5679318A Stable therapeutic radionuclide compositions and methods for preparation thereof 失效
标题翻译：稳定的治疗放射性核素组合物及其制备方法
公开(公告)号：US5679318A
公开(公告)日：1997-10-21
申请号：US342838
申请日：1994-11-21
申请人： Jean-Luc Vanderheyden , Alan R. Fritzberg , Joseph E. Bugaj , Fu-Min Su , Prasanna Venkatesan
发明人： Jean-Luc Vanderheyden , Alan R. Fritzberg , Joseph E. Bugaj , Fu-Min Su , Prasanna Venkatesan
IPC分类号： A61K51/04 , A61K51/10 , A61K51/12 , C07C227/08 , C07C271/22 , A61K51/00
CPC分类号： C07C271/22 , A61K51/0478 , A61K51/1093 , A61K51/12 , B82Y5/00 , C07C227/08 , A61K2123/00 , Y10S530/866
摘要： Stable therapeutic radionuclide compositions comprising, for example, .sup.186 Re, .sup.188 Re and .sup.131 I stably bound to a proteinaceous targeting moiety and suitable for human in vivo administration are disclosed. Stabilizing agents preferably comprise antioxidants and challenging agents, and combination of HSA with an antioxidant and/or challenging agent provides enhanced long term stability. Ascorbic acid is an especially preferred stabilizing agent, which provides stability of therapeutic radionuclide compositions at levels of at least about 90% for several hours up to several days.
摘要翻译：公开了稳定的治疗放射性核素组合物，其包含例如稳定结合蛋白质靶向部分并适于人体内施用的186Re，188Re和131I。稳定剂优选包含抗氧化剂和挑战性试剂，并且HSA与抗氧化剂和/或挑战性试剂的组合提供增强的长期稳定性。抗坏血酸是一种特别优选的稳定剂，其在至少约90％的水平下提供几个小时至几天的治疗性放射性核素组合物的稳定性。

4. 发明授权

US5393512A Stable therapeutic radionuclide compositions and methods for preparation thereof 失效
标题翻译：稳定的治疗放射性核素组合物及其制备方法
公开(公告)号：US5393512A
公开(公告)日：1995-02-28
申请号：US124359
申请日：1993-09-20
申请人： Jean-Luc Vanderheyden , Alan R. Fritzberg , Joseph E. Bugaj , Fu-Min Su , Prasanna Venkatesan
发明人： Jean-Luc Vanderheyden , Alan R. Fritzberg , Joseph E. Bugaj , Fu-Min Su , Prasanna Venkatesan
IPC分类号： A61K51/04 , A61K51/10 , A61K51/12 , C07C227/08 , C07C271/22 , A61K43/00 , A61K49/02
CPC分类号： C07C271/22 , A61K51/048 , A61K51/1093 , A61K51/12 , B82Y5/00 , C07C227/08 , A61K2123/00
摘要： Stable therapeutic radionuclide compositions comprising, for example, .sup.186 Re, .sup.188 Re and .sup.131 I stably bound to a proteinaceous targeting moiety and suitable for human in vivo administration are disclosed. Stabilizing agents preferably comprise antioxidants and challenging agents, and combination of HSA with an antioxidant and/or challenging agent provides enhanced long term stability. Ascorbic acid is an especially preferred stabilizing agent, which provides stability of therapeutic radionuclide compositions at levels of at least about 90% for several hours up to several days.
摘要翻译：公开了稳定的治疗放射性核素组合物，其包含例如稳定结合蛋白质靶向部分并适于人体内施用的186Re，188Re和131I。稳定剂优选包含抗氧化剂和挑战性试剂，并且HSA与抗氧化剂和/或挑战性试剂的组合提供增强的长期稳定性。抗坏血酸是一种特别优选的稳定剂，其在至少约90％的水平下提供几个小时至几天的治疗性放射性核素组合物的稳定性。

5. 发明授权

US4990787A Radionuclide generator system and method for its preparation and use 失效
标题翻译：放射性核素发生器系统及其制备和使用方法
公开(公告)号：US4990787A
公开(公告)日：1991-02-05
申请号：US416221
申请日：1989-09-29
申请人： Jean-Luc Vanderheyden , Fu-Min Su
发明人： Jean-Luc Vanderheyden , Fu-Min Su
IPC分类号： A61K51/12
CPC分类号： A61K51/1282 , A61K2121/00 , G21G1/0005
摘要： Improved radionuclide generators include a substantially insoluble salt of a parent radionuclide precursor which may be directly irradiated and then packed in a column for subsequent elution of the daughter radionuclide without the production of counter ion isotopic contaminants. The parent radionuclide precursor is provided in the form of an insoluble salt of the parent element whose counter ion, preferably aluminum, forms a relatively soluble salt with the desired daughter radionuclide. The improved generators may be prepared by reacting a parent radionuclide precursor with aluminum to obtain an aluminum salt of the precursor having low solubility in water, irradiating the aluminum salt to obtain an irradiated aluminum salt of the parent radionuclide, and then disposing the irradiated parent radionuclide in an elutable container. Useful parent radionuclide precursors include molybdenum-98 in the form of molybdate for the production of daughter .sup.99m Tc, as soluble pertechnetate, and tungsten-186 in the form of tungstate for the production of daughter .sup.188 Re as soluble perrhenate. The daughter .sup.99m Tc or .sup.188 Re may be eluting the generator matrix, e.g., with a saline solution.
摘要翻译：改进的放射性核素发生器包括母体放射性核素前体的基本上不溶的盐，其可以直接照射，然后包装在柱中，随后洗脱子内放射性核素而不产生抗衡离子同位素污染物。母体放射性核素前体以母体元素的不溶性盐的形式提供，其抗衡离子，优选为铝，与所需的儿子放射性核素形成相对可溶的盐。可以通过使母体放射性核素前体与铝反应来制备改进的发生器，以获得在水中具有低溶解度的前体的铝盐，照射铝盐以获得母体放射性核素的照射的铝盐，然后将照射的母体放射性核素在可洗涤的容器中。有用的母体放射性核素前体包括钼酸盐形式的钼-98，用于生产作为可溶性高锝酸盐的子体99mTc，钨酸盐形式的钨-186用于生产可溶性高铼酸盐的子188Re。子母99mTc或188Re可以例如用盐水溶液洗脱发生器基质。

6. 发明授权

US5656253A Ligands useful in radiographic imaging 失效
标题翻译：配体可用于放射成像
公开(公告)号：US5656253A
公开(公告)日：1997-08-12
申请号：US255148
申请日：1994-06-07
申请人： Raghavan Rajagopalan , Ananthachari Srinivasan , Jean-Luc Vanderheyden
发明人： Raghavan Rajagopalan , Ananthachari Srinivasan , Jean-Luc Vanderheyden
IPC分类号： A61K51/04 , A61K51/08 , C07B59/00 , C07D213/40 , C07D213/64 , C07D213/68 , C07F13/00 , C07K14/655 , C07K14/815 , A61K51/00 , A61K7/32 , C07D211/70 , C07D401/02
CPC分类号： C07K14/815 , A61K51/0478 , A61K51/088 , C07B59/004 , C07D213/40 , C07D213/64 , C07D213/68 , C07F13/005 , C07K14/6555 , A61K2121/00 , A61K2123/00
摘要： The present invention relates particularly to novel pyridine based nitrogen-sulfur ligands that are suitable for complexing with a radionuclide, and are useful as general imaging agents for diagnostic purposes, novel aminothiol ligands that are suitable for complexing with a radionuclide, and are useful as general imaging agents for diagnostic purposes, and amide-thiolate ligands having improved metal chelate formation kinetics. The amide-thiolate ligands include an amine which converts to a vinylogous amide upon complexation, thereby providing rapid complexation and thermodynamic stability. The ligands may be used for post formed labeling of biological substances for use in the fields of diagnosis and therapy.
摘要翻译：本发明特别涉及适用于与放射性核素络合的新型吡啶类氮硫配体，并且可用作诊断目的的一般成像剂，适于与放射性核素络合的新型氨基硫醇配体，并且可用作一般用于诊断目的的成像剂和具有改善的金属螯合物形成动力学的酰胺 - 硫醇酸配体。酰胺 - 硫醇酸酯配体包括在络合时转化为戊烯酰胺的胺，从而提供快速的络合和热力学稳定性。配体可用于生物物质的后期标记用于诊断和治疗领域。

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