公开(公告)号：US5387409A

公开(公告)日：1995-02-07

申请号：US818705

申请日：1992-01-07

Applicant: Adrian D. Nunn ,  Karen E. Linder ,  Silvia Jurisson ,  William C. Eckelman

Inventor： Adrian D. Nunn ,  Karen E. Linder ,  Silvia Jurisson ,  William C. Eckelman

IPC: G21G4/08 ,  A61K51/04 ,  C07F5/02 ,  C07F13/00 ,  C07J51/00 ,  A61K49/02 ,  A61K43/00

CPC classification number: C07J51/00 ,  A61K51/0478 ,  A61K51/0497 ,  C07F13/005 ,  C07F5/025 ,  A61K2123/00

Abstract: Boronic acid adducts of technetium-99m and radioactive rhenium dioxime complexes, each of which include biochemically active groups, are useful as diagnostic and therapeutic agents, respectively.

Abstract translation: 锝-99m的硼酸加成物和放射性铼二肟配合物，各自包括生化活性基团，分别可用作诊断和治疗剂。

公开(公告)号：US5354554A

公开(公告)日：1994-10-11

申请号：US824867

申请日：1992-01-22

Applicant: Stephen K. Rhind

Inventor： Stephen K. Rhind

IPC: A61K47/48 ,  A61K51/10 ,  A61K39/44 ,  A61K49/02 ,  C07K17/02

CPC classification number: A61K51/1087 ,  A61K47/48669 ,  A61K51/1093 ,  A61K2123/00 ,  Y10S435/972 ,  Y10S530/866

Abstract: Cross-linked labelled antibody conjugates are described which have at least one non-disulphide interchain bridge. The bridge may be the residue of a homo- or heterofunctional cross-linking reagent, and is located away from the antigen binding domains of the antibody. The antibody conjugates have an enhanced binding capacity and in vivo have good blood clearance and, in the presence of a tumour high tumour: blood and tumour: bone ratios. The conjugates are of use in the diagnosis and therapy of e.g. tumours and may be prepared by reaction of a cross-linking reagent with an antibody.

Abstract translation: 描述了具有至少一个非二硫键链间桥的交联标记的抗体缀合物。 桥可以是均相或异功能交联剂的残基，并且位于远离抗体的抗原结合结构域。 抗体缀合物具有增强的结合能力，并且在体内具有良好的血液清除率，并且在肿瘤高肿瘤：血液和肿瘤：骨比例的存在下。 缀合物可用于诊断和治疗例如 并且可以通过交联试剂与抗体的反应来制备。

公开(公告)号：US5312904A

公开(公告)日：1994-05-17

申请号：US879098

申请日：1992-05-04

Applicant: James D. Kelly ,  Kwok W. Chiu ,  David V. Griffiths ,  Jonathan R. Dilworth

Inventor： James D. Kelly ,  Kwok W. Chiu ,  David V. Griffiths ,  Jonathan R. Dilworth

IPC: A61K51/00 ,  A61K51/04 ,  C07F9/50 ,  C07F9/72 ,  C07F9/74 ,  C07F13/00 ,  A61K49/02

CPC classification number: C07F13/005 ,  A61K51/0478 ,  A61K2123/00

Abstract: Tridentate mono-anionic ligands have the structureX-A-Y-Q-Zwhere each of X and Y is independently P, As or N,Z is phenol, thiophenol or thiol, andA and Q are hydrocarbon linking groups.The ligands from cationic complexes with Technetium-99m, e.g. [Tc.sup.III K.sub.2 ].sup.+ where K is the ligand, having useful imaging properties.

Abstract translation: 三齿单阴离子配体具有结构X-A-Y-Q-Z，其中X和Y各自独立地为P，As或N，Z为苯酚，苯硫酚或硫醇，A和Q为烃连接基团。 来自与锝-99m的阳离子络合物的配体，例如 [TcIIIK2] +其中K是配体，具有有用的成像性质。

公开(公告)号：US5310539A

公开(公告)日：1994-05-10

申请号：US685937

申请日：1991-04-15

Applicant: Robert F. Williams

Inventor： Robert F. Williams

IPC: A61K49/00 ,  A61K49/08 ,  A61K49/14 ,  A61K49/16 ,  A61K51/00 ,  A61K51/08 ,  A61K49/02

CPC classification number: A61K49/128 ,  A61K49/085 ,  A61K51/06 ,  A61K2123/00

Abstract: The present invention involves an image-enhancing agent comprising melanin combined with an essentially non-dissociable signal-inducing metal. The signal-inducing metal has an association constant for its melanin combination of at least about 10.sup.20. Upon suspension or dissolution in water the metal remains undissociated. A preferred signal-inducing metal is paramagnetic or superparamagnetic, of course for magnetic resonance imaging. A preferred paramagnetic or superparamagnetic metals are gadolinium, iron, nickel, copper, erbium, europium, praseodymium, dysprosium, holmium, chromium or manganese. Gadolinium is the most effective metal. The metal is incorporated into the melanin in an ionic or particulate form. Metals may be utilized which are particularly useful to modify ultrasound images by the enhancement of the image obtained from emission and detection of high-frequency soundwaves. Metals emitting gamma particles may also be utilized to enhance images resulting from gamma particle emission scanning. .sup.51 Chromium, .sup.68 gallium, .sup.99m technitium and .sup.111 indium are preferred metals for gamma particle scanning. Additionally, native or synthesized melanin, in and of itself is an effective MRI image-enhancing agent.

Abstract translation: 本发明涉及包含黑色素与基本上不可解离的信号诱导金属组合的图像增强剂。 信号诱导金属具有至少约1020的黑色素组合的缔合常数。当悬浮或溶解在水中时，金属保持未解离。 优选的信号诱导金属当然是磁共振成像的顺磁性或超顺磁性。 优选的顺磁性或超顺磁性金属是钆，铁，镍，铜，铒，铕，镨，镝，钬，铬或锰。 钆是最有效的金属。 金属以离子或微粒形式并入黑色素。 可以利用通过增强从高频声波的发射和检测获得的图像来修改超声图像特别有用的金属。 也可以使用发射γ粒子的金属来增强由γ粒子发射扫描产生的图像。 51Chromium，68gallium，99mtechnitium和111indium是用于γ粒子扫描的优选金属。 此外，天然或合成的黑色素本身是一种有效的MRI图像增强剂。

公开(公告)号：US5310536A

公开(公告)日：1994-05-10

申请号：US832149

申请日：1992-02-06

Applicant: Ananthachari Srinivasan

Inventor： Ananthachari Srinivasan

IPC: A61K51/04 ,  A61K51/08 ,  C07D213/40 ,  C07D213/64 ,  C07D213/68 ,  C07F13/00 ,  A61K49/02 ,  A61K43/00

CPC classification number: C07F13/005 ,  A61K51/0478 ,  A61K51/088 ,  C07D213/40 ,  C07D213/64 ,  C07D213/68 ,  A61K2121/00 ,  A61K2123/00

Abstract: Amide-thiolate ligands having improved metal chelate formation kinetics are disclosed. The ligands include a tertiary amine strategically located to facilitate rapid formation of an amine-amide-thiolate intermediate complex, followed by transfer of the metal to a thermodynamically stable amide-thiolate complex. The amide-thiolate ligands of the present invention may be used for post formed labeling of biological substances for use in the fields of diagnosis and therapy.

Abstract translation: 公开了具有改进的金属螯合物形成动力学的酰胺 - 硫醇盐配体。 配体包括策略性定位以促进胺 - 酰胺 - 硫醇盐中间体复合物的快速形成，然后将金属转移到热力学稳定的酰胺 - 硫醇盐络合物的叔胺。 本发明的酰胺 - 硫醇酸酯配体可用于在诊断和治疗领域中用于生物物质的后成形标记。

公开(公告)号：US5302700A

公开(公告)日：1994-04-12

申请号：US197246

申请日：1988-05-23

Applicant: Michael R. Zalutsky ,  Acharan S. Narula

Inventor： Michael R. Zalutsky ,  Acharan S. Narula

IPC: A61K51/10 ,  C07B59/00 ,  G01N33/534 ,  C07K15/28 ,  A61K49/02 ,  C07K17/02

CPC classification number: C07B59/002 ,  A61K51/1093 ,  G01N33/534

Abstract: Compounds of the formulae, ##STR1## are provided where L is a linking group of the formula, ##STR2## is --Sn(n--C.sub.4 H.sub.9).sub.3 or --Sn(CH.sub.3).sub.3, HgCl or --N.sub.2.sup.+ ; R is hydrogen, methyl, mono-, di- or oligosaccharide; and R' is methyl. The compounds are site-specifically halogenated or radiohalogenated at the A group and coupled with macromolecules such as monoclonal antibodies, peptides or other proteins.

Abstract translation: 提供了下式的化合物，其中L是下式的连接基团，其中：＆lt; IMAGE＆gt;是-Sn（n-C4H9）3或-Sn（CH3）3，HgCl或-N2 +; R是氢，甲基，一，二或寡糖; 和R'是甲基。 该化合物在A组进行位点特异性卤化或放射性卤化，并与大分子如单克隆抗体，肽或其他蛋白质偶联。

公开(公告)号：US5277893A

公开(公告)日：1994-01-11

申请号：US864470

申请日：1992-04-06

Applicant: Buck A. Rhodes

Inventor： Buck A. Rhodes

IPC: A61K38/00 ,  A61K39/395 ,  A61K49/08 ,  A61K51/00 ,  A61K51/08 ,  A61K51/10 ,  C07K1/13 ,  C07K5/083 ,  C07K7/06 ,  C07K14/52 ,  C07K14/655 ,  C07K14/78 ,  C07K16/00 ,  G01N33/534 ,  G01N33/60 ,  A61K49/02 ,  A61K43/00

CPC classification number: A61K51/08 ,  A61K51/10 ,  C07K14/52 ,  C07K14/655 ,  C07K14/78 ,  C07K5/081 ,  C07K7/06 ,  A61K2121/00 ,  A61K2123/00 ,  A61K38/00

Abstract: Proteins containing one or more disulfide bonds are radiolabeled with radionuclides of technetium or rhenium for use in diagnosis and treatment of a variety of pathologic conditions. Radiolabeling is accomplished by partial reduction of the disulfide bonds of the protein using Sn (II), or using other reducing agents followed by the addition of Sn (II), removal of excess reducing agent and reduction by-products, and addition of a specified amount of pertechnetate or perrhenate reducing agent, such as stannous tartrate, with the addition accomplished in such a manner that further reduction of the protein is limited. The resulting product may be stored frozen or lyophilized, with radiolabeling accomplished by the addition of pertechnetate or perrhenate solution.

Abstract translation: 含有一个或多个二硫键的蛋白质用锝或铼的放射性核素进行放射性标记，用于诊断和治疗各种病理状况。 放射性标记是通过使用Sn（II）部分还原蛋白质的二硫键，或使用其它还原剂，然后加入Sn（II），除去过量的还原剂和还原副产物，并加入指定的 高铁酸盐或高铼酸盐还原剂的量，例如酒石酸亚锡，其加入以限制蛋白质的进一步还原的方式进行。 所得产物可以冷冻或冻干，通过加入高锝酸盐或高铼酸盐溶液进行放射性标记。

公开(公告)号：US5277892A

公开(公告)日：1994-01-11

申请号：US840076

申请日：1992-02-20

Applicant: Buck A. Rhodes

Inventor： Buck A. Rhodes

IPC: A61K38/00 ,  A61K49/08 ,  A61K51/08 ,  A61K51/10 ,  C07K5/083 ,  C07K7/06 ,  C07K14/52 ,  C07K14/655 ,  C07K14/78 ,  A61K49/02 ,  A61K49/00

CPC classification number: C07K14/78 ,  A61K49/085 ,  A61K49/14 ,  A61K51/08 ,  A61K51/088 ,  C07K14/52 ,  C07K14/655 ,  C07K5/081 ,  C07K7/06 ,  A61K2121/00 ,  A61K2123/00 ,  A61K38/00

Abstract: Methods and reagents for the in vivo tagging of leukocytes, and in particular lymphocytes with a leukostimulatory agent and a linked medically useful metal ion, including a radioisotope, and subsequent detection of leukocyte or lymphocyte trafficking and sites of concentrated leukocytes or lympLICENSE RIGHTSThe U.S. Government has a paid-up license in this invention and the right in limited circumstances to require the patent owner to license others on reasonable terms as provided for by the terms of Small Business Innovative Research Grant No. 1 R43 AR41124 awarded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Department of Health and Human Services.

Abstract translation: 用于体内标记白细胞的方法和试剂，特别是具有白细胞促进剂和连接的医学上有用的金属离子（包括放射性同位素）的淋巴细胞，以及随后检测白细胞或淋巴细胞运输以及患者内浓缩的白细胞或淋巴细胞的位点。 公开了放射性检测或顺磁性手段。

公开(公告)号：US5273738A

公开(公告)日：1993-12-28

申请号：US562127

申请日：1990-03-03

Applicant: Dana C. Matthews ,  Irwin D. Bernstein ,  John A. Hansen ,  Fred R. Appelbaum ,  Claudio Anasetti ,  Paul J. Martin

Inventor： Dana C. Matthews ,  Irwin D. Bernstein ,  John A. Hansen ,  Fred R. Appelbaum ,  Claudio Anasetti ,  Paul J. Martin

IPC: A61K51/10 ,  A61K43/00 ,  A61K49/02

CPC classification number: A61K51/1027

Abstract: A method of selectively delivering radiation homogeneously to lymphoid and marrow tissues in vivo including the step of administering an effective dose of a radiolabeled immunological binding partner of a T-200 antigen to a patient is disclosed. Also disclosed are immunological binding partners and compositions based thereon for carrying out the method.

Abstract translation: 公开了一种在体内选择性地将辐射均匀地递送到淋巴和骨髓组织的方法，包括向患者施用有效剂量的T-200抗原的放射性标记的免疫结合配偶体的步骤。 还公开了免疫结合配偶体和基于其的用于实施该方法的组合物。

公开(公告)号：US5268163A

公开(公告)日：1993-12-07

申请号：US934648

申请日：1992-08-21

Applicant: Alfons Verbruggen

Inventor： Alfons Verbruggen

IPC: A61K51/00 ,  A61K51/04 ,  C07B59/00 ,  C07F13/00 ,  A61K49/02

CPC classification number: A61K51/04 ,  A61K51/00

Abstract: The invention relates to a method of preparing a radiolabelled technetium complex by bringing Tc-99m in the form of a pertechnetate solution in a complex-forming reaction with a compound of the general formula ##STR1## wherein R.sub.1 -R.sub.12 each independently represents a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group, a carboxy group, or a carboxy(C.sub.1 -C.sub.4)alkyl group;or whereinR.sub.1 +R.sub.2, R.sub.3 +R.sub.4, R.sub.5 +R.sub.6, R.sub.7 +R.sub.8, R.sub.9 +R.sub.10 and R.sub.11 +R.sub.12 each independently represent an oxo or imino function;and wherein furthermore:R.sub.13 is a hydrogen atom, a C.sub.1 -C.sub.4 alkyl group or a carboxy(C.sub.1 -C.sub.4)alkyl group;R.sub.14 is a hydrogen atom or an amino group; n is 0, 1 or 2;A represents an amino group or a mercapto group; andB represents a mercapto group, or a group of the general formula NH--Z--CO--NH--.sub.m Z--COOH, wherein:Z is an optionally substituted C.sub.1 -C.sub.4 alkylene, cycloalkylene or alkylidene group, andm is an integer from 0 to 20;with the provisos:(i) that at least one substituent selected from the group consisting of R.sub.1 -R.sub.13 and B is or comprise a carboxy group; and(ii) that R.sub.3 +R.sub.4 or R.sub.7 +R.sub.8 represents an oxo function or both R.sub.3 +R.sub.4 and R.sub.7 +R.sub.8 or both R.sub.5 +R.sub.6 and R.sub.7 +R.sub.8 represent oxo functions, if A is an amino group and B is a group of the formula NH--Z--CO--NH--.sub.m Z--COOH; by performing said reaction in the presence of Sn(II) as a reducing agent, in the absence of a transfer agent, in an at least substantially aqueous solvent system having a pH of at least 10, and at ambient temperature.The invention further relates to a kit for performing said method.

Abstract translation: PCT No.PCT / US91 / 02450 Sec。 371日期：1992年8月21日 102（e）日期1992年8月21日PCT 1991年4月10日PCT。本发明涉及一种制备放射性标记锝络合物的方法，其中将Tc-99m以高锝酸盐溶液的形式与络合物形成反应 其中R1-R12各自独立地表示氢原子，C1-C4烷基，羧基或羧基（C1-C4）烷基的通式（I）的化合物。 或其中R 1 + R 2，R 3 + R 4，R 5 + R 6，R 7 + R 8，R 9 + R 10和R 11 + R 12各自独立地表示氧代或亚氨基官能团; 并且其中R 13为氢原子，C 1 -C 4烷基或羧基（C 1 -C 4）烷基; R14是氢原子或氨基; n为0,1或2; A表示氨基或巯基; B表示巯基，或通式为NH-Z-CO-NH-mZ-COOH的基团，其中：Z为任选取代的C 1 -C 4亚烷基，亚环烷基或亚烷基，m为0 到20 条件是：（i）至少一个选自R 1 -R 13和B的取代基是或包含羧基; 和（ii）R3 + R4或R7 + R8代表氧代功能或R3 + R4和R7 + R8两者，或者R5 + R6和R7 + R8两者均代表氧代功能，如果A是氨基，B是一组 式NH-Z-CO-NH-mZ-COOH; 在不存在转移剂的情况下，在Sn（II）作为还原剂存在下，在pH至少为10的至少基本上为水的溶剂体系中和在环境温度下进行所述反应。 本发明还涉及一种用于执行所述方法的套件。