公开(公告)号：US07741121B2

公开(公告)日：2010-06-22

申请号：US11895636

申请日：2007-08-23

Applicant: Arkadij M Elizarov ,  Hartmuth C. Kolb ,  Jianzhong Zhang

Inventor： Arkadij M Elizarov ,  Hartmuth C. Kolb ,  Jianzhong Zhang

IPC: G01N23/00

CPC classification number: G01N30/88 ,  C07B59/00 ,  C07B63/00 ,  G01N30/82 ,  G01N2030/77 ,  G01N2030/8809 ,  Y10T137/86493 ,  Y10T436/11 ,  Y10T436/115831 ,  G01N30/6095

Abstract: The present application is generally directed to microfluidic devices and methods for the achievement and assessment of chemical and radiochemical purity of (microfluidic) radio-synthesis products. More particularly, the current application relates to systems for purification and analysis of radiochemical products yielded by microfluidic synthesis devices.

Abstract translation: 本申请通常涉及用于实现和评估（微流体）放射合成产物的化学和放射化学纯度的微流体装置和方法。 更具体地，本申请涉及用于净化和分析由微流体合成装置产生的放射化学产物的系统。

公开(公告)号：US20090010846A1

公开(公告)日：2009-01-08

申请号：US12098390

申请日：2008-04-04

Applicant: Hartmuth C. Kolb ,  Joseph C. Walsh ,  Umesh B. Gangadharmath ,  Farhad Karimi ,  Henry Clifton Padgett ,  Dhanalakshmi Kasi ,  Zhiyong Gao ,  Qianwa Liang ,  Thomas Lee Collier ,  Brian A. Duclos ,  Tieming Zhao

Inventor： Hartmuth C. Kolb ,  Joseph C. Walsh ,  Umesh B. Gangadharmath ,  Farhad Karimi ,  Henry Clifton Padgett ,  Dhanalakshmi Kasi ,  Zhiyong Gao ,  Qianwa Liang ,  Thomas Lee Collier ,  Brian A. Duclos ,  Tieming Zhao

IPC: A61K51/04 ,  C07D403/12 ,  A61P35/00

CPC classification number: C07D403/06 ,  C07B59/002 ,  C07D403/12

Abstract: The present invention relates to novel radioactively labeled bioreducible tracers of Formula I useful for detecting hypoxic tumors or ischemic tissue in vivo. In one embodiment, the tracers consist of a 2-nitroimidazole moiety, a triazole, metabolically stable linker with pharmacokinetics enhancing substituents, and a radioisotope. The preferred in vivo imaging modality is positron emission tomography.

Abstract translation: 本发明涉及用于体内检测缺氧性肿瘤或缺血组织的式I的新型放射性标记的生物可降解示踪剂。 在一个实施方案中，示踪剂由2-硝基咪唑部分，三唑，具有药代动力学增强取代基的代谢稳定接头和放射性同位素组成。 优选的体内成像模式是正电子发射断层摄影。

公开(公告)号：US20080233018A1

公开(公告)日：2008-09-25

申请号：US12011220

申请日：2008-01-23

Applicant: Robert Michael van Dam ,  Carroll Edward Ball ,  Arkadij M. Elizarov ,  Hartmuth C. Kolb

Inventor： Robert Michael van Dam ,  Carroll Edward Ball ,  Arkadij M. Elizarov ,  Hartmuth C. Kolb

IPC: B01J19/00 ,  C07H1/00

CPC classification number: B01J19/0093 ,  B01J2219/00783 ,  B01J2219/00826 ,  B01J2219/00831 ,  B01J2219/00833 ,  B01J2219/0086 ,  B01J2219/00873 ,  B01J2219/00891 ,  B01J2219/00907 ,  B01J2219/00909 ,  B01J2219/00952 ,  B01J2219/00959 ,  B01J2219/00961 ,  B01J2219/00963 ,  B01J2219/00986 ,  B01J2219/0099 ,  C07B59/005

Abstract: The present application relates to microfluidic devices and related technologies, and to chemical processes using such devices. More specifically, the application discloses a fully automated synthesis of radioactive compounds for imaging, such as by positron emission tomography (PET), in a fast, efficient and compact manner. In particular, this application describe an automated, stand-alone, microfluidic instrument for the multi-step chemical synthesis of radiopharmaceuticals, such as probes for PET and a method of using such instruments.

Abstract translation: 本申请涉及微流体装置和相关技术，以及使用这种装置的化学过程。 更具体地，本申请公开了以快速，有效和紧凑的方式例如通过正电子发射断层摄影（PET）来成像的放射性化合物的全自动合成。 特别地，本申请描述了用于放射性药物的多步化学合成的自动化，独立的微流体仪器，例如用于PET的探针和使用这种仪器的方法。

公开(公告)号：US08658112B2

公开(公告)日：2014-02-25

申请号：US13286418

申请日：2011-11-01

Applicant: Arkadij M. Elizarov ,  Hartmuth C. Kolb ,  R. Michael Van Dam ,  James R. Heath

Inventor： Arkadij M. Elizarov ,  Hartmuth C. Kolb ,  R. Michael Van Dam ,  James R. Heath

IPC: G01N33/00

CPC classification number: B01F11/0042 ,  B01F11/0071 ,  B01F13/0059 ,  B01J19/0093 ,  B01J2219/00286 ,  B01J2219/00396 ,  B01J2219/00398 ,  B01J2219/00414 ,  B01J2219/00418 ,  B01J2219/00495 ,  B01J2219/00585 ,  B01J2219/00599 ,  B01J2219/00731 ,  B01J2219/00759 ,  B01J2219/00783 ,  B01J2219/00788 ,  B01J2219/00822 ,  B01J2219/00824 ,  B01J2219/00826 ,  B01J2219/00828 ,  B01J2219/00831 ,  B01J2219/00833 ,  B01J2219/00858 ,  B01J2219/0086 ,  B01J2219/00862 ,  B01J2219/00873 ,  B01J2219/00889 ,  B01J2219/00891 ,  B01J2219/00907 ,  B01J2219/00916 ,  B01J2219/00927 ,  B01J2219/00986

Abstract: Described herein are automated, integrated microfluidic device comprising a chemical reaction chip comprising for performing chemical reaction, a microscale column integrated with the chip and configured for liquid flow from the column to at least one flow channel, and wherein the fluid flow into the column is controlled by on-chip valves; and comprising at least two on-chip valves for controlling fluid flow in the microfluidic device.

Abstract translation: 本文描述的是包括用于进行化学反应的化学反应芯片的自动化集成微流体装置，与芯片集成的微量柱，并且构造成用于从柱流到至少一个流动通道的液体流，并且其中流入塔的流体流是 由片上阀控制; 并且包括用于控制微流体装置中的流体流动的至少两个片上阀。

公开(公告)号：US08420052B2

公开(公告)日：2013-04-16

申请号：US12509259

申请日：2009-07-24

Applicant: Hartmuth C. Kolb ,  Joseph C. Walsh ,  Wei Zhang ,  Umesh B. Gangadharmath ,  Dhanalakshmi Kasi ,  Kai Chen ,  Anjana Sinha ,  Eric Wang ,  Gang Chen ,  Peter J. H. Scott ,  Henry Clifton Padgett ,  Qianwa Liang ,  Zhiyong Gao ,  Tieming Zhao ,  Chunfang Xia ,  Vani P. Mocharla

Inventor： Hartmuth C. Kolb ,  Joseph C. Walsh ,  Wei Zhang ,  Umesh B. Gangadharmath ,  Dhanalakshmi Kasi ,  Kai Chen ,  Anjana Sinha ,  Eric Wang ,  Gang Chen ,  Peter J. H. Scott ,  Henry Clifton Padgett ,  Qianwa Liang ,  Zhiyong Gao ,  Tieming Zhao ,  Chunfang Xia ,  Vani P. Mocharla

IPC: A61K51/00 ,  A61M36/14

CPC classification number: C07D417/14 ,  A61K51/0406 ,  A61K51/0453 ,  A61K51/0455 ,  A61K51/0459 ,  C07D277/64 ,  C07D277/68 ,  C07D417/04 ,  C07D471/04 ,  C07D498/14 ,  C07D513/04 ,  C07D513/14

Abstract: Provided herein are compounds and compositions which comprise the formulae as disclosed herein, wherein the compound is an amyloid binding compound. An amyloid binding compound according to the invention may be administered to a patient in amounts suitable for in vivo imaging of amyloid deposits, and distinguish between neurological tissue with amyloid deposits and normal neurological tissue. Amyloid probes of the invention may be used to detect and quantitate amyloid deposits in diseases including, for example, Down's syndrome, familial Alzheimer's Disease. In another embodiment, the compounds may be used in the treatment or prophylaxis of neurodegenerative disorders. Also provided herein are methods of allowing the compound to distribute into the brain tissue, and imaging the brain tissue, wherein an increase in binding of the compound to the brain tissue compared to a normal control level of binding indicates that the mammal is suffering from or is at risk of developing a neurodegenerative disease.

Abstract translation: 本文提供了包含本文公开的式的化合物和组合物，其中所述化合物是淀粉样蛋白结合化合物。 根据本发明的淀粉样蛋白结合化合物可以以适于淀粉样蛋白沉积物的体内成像的量施用于患者，并且可以区分具有淀粉样沉积物的神经组织和正常神经组织。 本发明的淀粉样蛋白探针可用于检测和定量疾病中的淀粉样蛋白沉积物，包括例如唐氏综合症，家族性阿尔茨海默氏病。 在另一个实施方案中，所述化合物可用于治疗或预防神经变性疾病。 本文还提供了允许化合物分布到脑组织中并对脑组织成像的方法，其中与正常对照结合水平相比，化合物与脑组织的结合增加指示哺乳动物患有或 有发展神经变性疾病的风险。

公开(公告)号：US20120283490A1

公开(公告)日：2012-11-08

申请号：US13445147

申请日：2012-04-12

Applicant: Umesh B. Gangadharmath ,  Joseph C. Walsh ,  Hartmuth C. Kolb ,  Ricardo Rodriguez ,  Arkadij M. Elizarov ,  Carroll Edward Ball

Inventor： Umesh B. Gangadharmath ,  Joseph C. Walsh ,  Hartmuth C. Kolb ,  Ricardo Rodriguez ,  Arkadij M. Elizarov ,  Carroll Edward Ball

IPC: C07C17/04 ,  F04D13/00 ,  B01J19/00

CPC classification number: B01J19/004 ,  A61K51/0455 ,  A61K51/08 ,  A61K51/082 ,  B01J4/008 ,  C07B59/00 ,  Y10T137/86035

Abstract: A system, apparatus, and method for transferring chemical solutions and synthesizing a tracer. For transferring chemical solutions, the system comprises a primary container; a secondary container; a first line in communication with the primary container and the secondary container. The first line facilitates the flow of gas and/or liquid between the primary container and the secondary container. A valve located upstream of the secondary container and downstream of the primary container regulates flow within the first line; a second line in communication with the secondary container. For synthesizing a tracer, the system includes a source of a solution having a radionuclide. A first container has a tracer precursor and is in communication with the source of solution.

Abstract translation: 用于转移化学溶液并合成示踪剂的系统，装置和方法。 为了转移化学溶液，该系统包括主容器; 次级容器 与第一容器和次容器连通的第一线。 第一行有利于主容器和次容器之间的气体和/或液体的流动。 位于次级容器上游并且在主容器下游的阀调节第一管线内的流动; 与第二容器通信的第二行。 为了合成示踪剂，该系统包括具有放射性核素的溶液源。 第一容器具有示踪剂前体并与溶液源连通。

公开(公告)号：US08293206B2

公开(公告)日：2012-10-23

申请号：US12455346

申请日：2009-06-01

Applicant: Hartmuth C. Kolb ,  Joseph C. Walsh ,  Kai Chen ,  Dhanalakshmi Kasi ,  Umesh B. Gangadharmath ,  Peter J. H. Scott ,  Gang Chen ,  Vani P. Mocharla

Inventor： Hartmuth C. Kolb ,  Joseph C. Walsh ,  Kai Chen ,  Dhanalakshmi Kasi ,  Umesh B. Gangadharmath ,  Peter J. H. Scott ,  Gang Chen ,  Vani P. Mocharla

IPC: A61M36/14 ,  A61K39/00

CPC classification number: A61K51/088 ,  A61K51/082

Abstract: The present disclosure provides methods for treating cancer in a patient in need of such treatment, the method includes prequalifying a patient's therapeutic treatment by performing a molecular imaging procedure to the patient using a labeled biomarker specific for a cancer target at the tumor site; and administering a therapeutic effective amount of a compound comprising a targeting agent linked to a chemotherapeutic or a targeting agent linked to an antibody. Embodiments of the present invention also include compounds and compositions for using such methods.

Abstract translation: 本公开提供了在需要这种治疗的患者中治疗癌症的方法，所述方法包括通过使用在肿瘤部位对癌症靶标特异的标记的生物标志物向患者进行分子成像程序来资格评估患者的治疗性治疗; 以及施用治疗有效量的包含连接于与抗体连接的化学治疗剂或靶向剂的靶向剂的化合物。 本发明的实施方案还包括使用这些方法的化合物和组合物。

公开(公告)号：US08214159B2

公开(公告)日：2012-07-03

申请号：US12630298

申请日：2009-12-03

Applicant: Jianzhong Zhang ,  Arkadij M. Elizarov ,  Reza Miraghaie ,  Carroll Edward Ball ,  Hartmuth C. Kolb

Inventor： Jianzhong Zhang ,  Arkadij M. Elizarov ,  Reza Miraghaie ,  Carroll Edward Ball ,  Hartmuth C. Kolb

IPC: G01N31/00

CPC classification number: G01N35/00663 ,  G01N15/06 ,  G01N2030/8804 ,  G01N2033/0093

Abstract: Methods and apparatus to assess current aspects of Quality Control useful for release of radioactive compounds for imaging, such as PET tracers as injectables, in an automated manner, without user interference, and in compliance with regulatory guidelines. The present method and system relates to an integrated automated quality control analysis of a substance utilizing a single sample injection for a plurality of inline quality control tests. A quantitative analysis of the sample via the plurality of quality control tests is conducted. A measurement value of each of the plurality of quality control parameters is determined and a comparison of each measurement value of the plurality of quality control parameters with a predetermined corresponding criterion value is made. A cumulative quality rating for the sample is determined and the validated sample is released based on the quality rating.

Abstract translation: 评估用于成像放射性化合物释放的当前质量控制方法和装置，例如作为注射剂的PET示踪剂，以自动方式，无需用户干扰，并符合法规。 本方法和系统涉及使用单个样品注入用于多个在线质量控制测试的物质的综合自动化质量控制分析。 通过多次质量控制测试对样品进行定量分析。 确定多个质量控制参数中的每一个的测量值，并且进行多个质量控制参数的每个测量值与预定的对应标准值的比较。 确定样品的累积质量等级，并根据质量评级释放验证的样品。

公开(公告)号：US08071035B2

公开(公告)日：2011-12-06

申请号：US12102822

申请日：2008-04-14

Applicant: Arkadij M Elizarov ,  Carroll Edward Ball ,  Jianzhong Zhang ,  Hartmuth C. Kolb ,  R. Michael Van Dam ,  Lawrence Talcott Diener ,  Sean Ford ,  Reza Miraghaie

Inventor： Arkadij M Elizarov ,  Carroll Edward Ball ,  Jianzhong Zhang ,  Hartmuth C. Kolb ,  R. Michael Van Dam ,  Lawrence Talcott Diener ,  Sean Ford ,  Reza Miraghaie

IPC: G21C1/00 ,  B01J19/00 ,  B01J10/00 ,  B01L3/00 ,  B01L3/02 ,  F16K3/00

CPC classification number: C07H5/02 ,  B01J19/0093 ,  B01J2219/00783 ,  B01J2219/0086 ,  B01J2219/00873 ,  B01J2219/00891 ,  B01J2219/00907 ,  B01J2219/00909

Abstract: Methods and devices for a fully automated synthesis of radioactive compounds for imaging, such as by positron emission tomography (PET), in a fast, efficient and compact manner are disclosed. In particular, the various embodiments of the present invention provide an automated, stand-alone, hands-free operation of the entire radiosynthesis cycle on a microfluidic device with unrestricted gas flow through the reactor, starting with target water and yielding purified PET radiotracer within a period of time shorter than conventional chemistry systems. Accordingly, one aspect of the present invention is related to a microfluidic chip for radiosynthesis of a radiolabeled compound, comprising a reaction chamber, one or more flow channels connected to the reaction chamber, one or more vents connected to said reaction chamber, and one or more integrated valves to effect flow control in and out of said reaction chamber.

Abstract translation: 公开了以快速，有效和紧凑的方式全面自动合成用于成像的放射性化合物的方法和装置，例如通过正电子发射断层摄影（PET）。 特别地，本发明的各种实施例提供了在具有不受限制的气流通过反应器的微流体装置上的整个放射合成循环的自动化的，独立的，免手操作的操作，从目标水开始并产生纯化的PET放射性示踪器 时间比传统化学系统短。 因此，本发明的一个方面涉及用于放射性标记的化合物的放射合成的微流体芯片，包括反应室，连接到反应室的一个或多个流动通道，连接到所述反应室的一个或多个通气口，以及一个或多个 更一体化的阀来实现进出所述反应室的流量控制。

公开(公告)号：US20110098465A1

公开(公告)日：2011-04-28

申请号：US12968466

申请日：2010-12-15

Applicant: Carroll Edward Ball ,  Arkadij M. Elizarov ,  Hartmuth C. Kolb

Inventor： Carroll Edward Ball ,  Arkadij M. Elizarov ,  Hartmuth C. Kolb

IPC: C07H1/00

CPC classification number: B01J19/0093 ,  B01F5/0057 ,  B01F5/0068 ,  B01F13/0059 ,  B01J2219/00788 ,  B01J2219/00862 ,  B01J2219/00873 ,  B01J2219/00889 ,  C07B59/00 ,  Y10T436/115831

Abstract: Methods and apparatus for facilitating the synthesis of compounds in a nonflow-through device are presented. Application of the nonflow-through methods and microfluidic devices to the synthesis of radiolabeled compounds is described. These methods and apparatus enable the introduction of a pressurized gas through a tangential slit into a vortex reactor of the nonflow-through device, while one or more liquids are delivered to the reaction chamber through the same or different inlet ports. The introduction of the pressurized gas produces a cyclonic motion of the mixture within the reactor. Such a mechanism may be used to facilitate the evaporation of various liquids within the reactor at lower temperatures, thus reducing the production of unwanted byproducts that are associated with the use of high temperatures. In addition, thorough mixing of various liquids may be effected rapidly while allowing chemical reactions to take place efficiently within the vortex reactor.

Abstract translation: 提出了促进非通流装置中化合物合成的方法和装置。 描述了将非流通方法和微流体装置应用于放射性标记化合物的合成。 这些方法和装置能够通过切向狭缝将加压气体引入非流通装置的涡流反应器中，同时一个或多个液体通过相同或不同的入口输送到反应室。 加压气体的引入在反应器内产生混合物的旋风运动。 这种机理可以用于促进在较低温度下反应器内的各种液体的蒸发，从而减少与使用高温相关的不需要的副产物的产生。 此外，可以快速实施各种液体的充分混合，同时允许在涡流反应器内有效地发生化学反应。