[68Ga]NODAGA-RGD([68Ga]NODAGA-RGD) - 药物靶点：αvβ3_在研适应症：颈动脉疾病，炎症，动脉粥样硬化斑块_专利_临床

概要

基本信息

药物类型

多肽偶联核素、诊断用放射药物

别名

靶点

αvβ3

作用方式

拮抗剂

作用机制

αvβ3拮抗剂(整合素α-V/β-3复合体拮抗剂)

治疗领域

神经系统疾病心血管疾病其他疾病

在研适应症

颈动脉疾病炎症动脉粥样硬化斑块

非在研适应症-

原研机构

Medical University of Innsbruck

在研机构

Centre Hospitalier Universitaire Vaudois

非在研机构-

权益机构-

最高研发阶段临床1/2期

首次获批日期-

最高研发阶段(中国)-

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关联

3

项与 [68Ga]NODAGA-RGD 相关的临床试验

EUCTR2014-004392-23-FI

/ Not yet recruiting临床2期IIT

68Ga-NODAGA-RGD cardiac PET in patients with acute myocardial infarction or chronic total coronary occlusion

开始日期2018-02-08

申办/合作机构

Turku University Hospital

EUCTR2013-003741-42-AT

/ Not yet recruiting临床1/2期IIT

PROSPECTIVE STUDY OF [68GA]NODAGA-RGD-PET FOR THE DIAGNOSIS OF HEPATOCELLULAR CARCINOMA AND THE ASSESSMENT OF TREATMENT RESPONSE

开始日期2014-05-06

申办/合作机构-

NCT01608516

/ Recruiting临床1/2期IIT

Multimodal Assessment of the Inflammatory Atheromatous Plaque : Comparison Between 68Ga-NODAGA-RGD PET/CT, 18F-FDG PET/CT, MRI AND US

The present study aims at assessing the ability of 68Ga-NODAGA-RGD PET/CT for the detection of inflammatory atheromatous plaques in the carotid arteries, compared to 18F-FDG PET/CT, MRI and US and to determine the contribution of each imaging technique. Current gold standard for inflammation is histopathology.
Hypothesis : 68Ga-NODAGA-RGD might give a better initial evaluation of patients with atheromatous plaques in the carotid artery eligible for endarterectomy.

开始日期2012-04-01

申办/合作机构

Centre Hospitalier Universitaire Vaudois

100 项与 [68Ga]NODAGA-RGD 相关的临床结果

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100 项与 [68Ga]NODAGA-RGD 相关的转化医学

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100 项与 [68Ga]NODAGA-RGD 相关的专利（医药）

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3

项与 [68Ga]NODAGA-RGD 相关的文献（医药）

2016-10-01·Molecular Imaging and Biology3区 · 医学

Comparison of Ga-68-Labeled Fusarinine C-Based Multivalent RGD Conjugates and [68Ga]NODAGA-RGD—In Vivo Imaging Studies in Human Xenograft Tumors

3区 · 医学

Article

作者: Petrik, Milos ; Laverman, Peter ; Decristoforo, Clemens ; Haubner, Roland ; Zhai, Chuangyan ; Rangger, Christine ; Haas, Hubertus ; Franssen, Gerben M ; Summer, Dominik

PURPOSEMultimeric arginine-glycine-aspartic acid (RGD) peptides have advantages for imaging integrin αvβ3 expression. Here, we compared the in vitro and in vivo behavior of three different Ga-68-labeled multimeric Fusarinine C-RGD (FSC-RGD) conjugates, whereby RGD was coupled directly, via a succinic acid or PEG linker (FSC(RGDfE)3, FSC(succ-RGD)3, FSC(Mal-RGD)3). The positron emission tomography/X-ray computed tomography (PET/CT) imaging properties were further compared using [(68)Ga]FSC(succ-RGD)3 with the monomeric [(68)Ga]NODAGA-RGD in a murine tumor model.PROCEDUREFSC-RGD conjugates were labeled with Ga-68, and stability properties were studied. For in vitro characterization, the partition coefficient, integrin αvβ3 binding affinity, and cell uptake were determined. To characterize the in vivo properties, biodistribution studies and microPET/CT were carried out using mice bearing either human M21/M21-L melanoma or human U87MG glioblastoma tumor xenografts.RESULTSAll FSC-RGD conjugates were quantitatively labeled with Ga-68 within 10 min at RT. The [(68)Ga]FSC-RGD conjugates exhibited high stability and hydrophilic character, with only minor differences between the different conjugates. In vitro and in vivo studies showed enhanced integrin αvβ3 binding affinity, receptor-selective tumor uptake, and rapid renal excretion resulting in good imaging properties.CONCLUSIONSThe type of linker between FSC and RGD had no pronounced effect on targeting properties of [(68)Ga]FSC-RGD trimers. In particular, [(68)Ga]FSC(succ-RGD)3 exhibited improved properties compared to [(68)Ga]NODAGA-RGD, making it an alternative for imaging integrin αvβ3 expression.

2013-01-01·Nuclear Medicine and Biology4区 · 医学

[68Ga]NS3-RGD and [68Ga] Oxo-DO3A-RGD for imaging αvβ3 integrin expression: synthesis, evaluation, and comparison

4区 · 医学

Article

作者: Clemens Decristoforo ; Milos Petrik ; Roland Haubner ; Irene Virgolini ; Christine Rangger ; Gesine Seidel ; Hans-Jürgen Pietzsch ; Peter A. Knetsch

INTRODUCTION⁶⁸Ga-labeled RGD peptides in combination with PET allow non-invasive determination of α(v)β₃ integrin expression which is highly increased during tumor-induced angiogenesis. The aim of this study was to synthesize and evaluate two RGD peptides containing alternative chelating systems, namely [⁶⁸Ga]NS₃-RGD-RGD and [⁶⁸Ga]Oxo-DO3A-RGD and to compare their in vitro and in vivo properties with [⁶⁸Ga]DOTA- and [⁶⁸Ga]NODAGA-RGD.METHODSSyntheses of both radiotracers followed standard SPPS protocols. For in vitro characterization distribution coefficients, protein binding abilities, serum stabilities, and α(v)β₃ integrin binding affinities were determined. For in vitro tests as well as for the biodistribution assay α(v)β₃ positive human melanoma M21 and α(v)β₃ negative M21-L cells were used.RESULTS⁶⁸Ga-labeling of NS₃-RGD resulted in good radiochemical purity, whereas HPLC analysis showed two peaks with a ratio of 1:6 for [⁶⁸Ga]Oxo-DO3A-RGD. Distribution coefficients were -3.4 for [⁶⁸Ga]Oxo-DO3A-RGD and -2.9 for [⁶⁸Ga]NS₃-RGD. Both radiotracers were stable in PBS solution at 37°C for 2 h but lack stability in human serum. Protein binding was approximately 40% of the total activity for [⁶⁸Ga]NS₃-RGD and 70% for [⁶⁸Ga]Oxo-DO3A-RGD, respectively, resulting in high blood pool activities. Biodistribution assays confirmed these findings and showed an additional high uptake in liver and kidneys, especially for [⁶⁸Ga]NS₃-RGD. Furthermore, [⁶⁸Ga]Oxo-DO3A-RGD showed nearly the same activity concentrations in α(v)β₃ positive and α(v)β₃ negative tumors.CONCLUSIONS[⁶⁸Ga]Oxo-DO3A-RGD and [⁶⁸Ga]NS₃-RGD have inferior characteristics compared to already existing ⁶⁸Ga-labeled RGD peptides and thus, both are not suited to image α(v)β₃ integrin expression. Of all our tested RGD peptides, [⁶⁸Ga]NODAGA-RGD still possesses the most favorable imaging properties. Moreover this study shows that the use of appropriate chelators to achieve good targeting properties of ⁶⁸Ga-labeled biomolecules and careful in vitro and in vivo evaluation including comparative studies of different strategies are essential components in designing an effective imaging agent for PET.

2011-07-01·European Journal of Nuclear Medicine and Molecular Imaging

[68Ga]NODAGA-RGD for imaging αvβ3 integrin expression

Article

作者: Guggenberg, Elisabeth ; Pichler, Bernd J. ; Kesenheimer, Christian ; Haubner, Roland ; Petrik, Milos ; Decristoforo, Clemens ; Virgolini, Irene ; Rangger, Christine ; Griessinger, Christoph M. ; Fani, Melpomeni ; Knetsch, Peter A.

PURPOSEA molecular target involved in the angiogenic process is the α(v)β(3) integrin. It has been demonstrated in preclinical as well as in clinical studies that radiolabelled RGD peptides and positron emission tomography (PET) allow noninvasive monitoring of α(v)β(3) expression. Here we introduce a (68)Ga-labelled NOTA-conjugated RGD peptide ([(68)Ga]NODAGA-RGD) and compare its imaging properties with [(68)Ga]DOTA-RGD using small animal PET.METHODSSynthesis of c(RGDfK(NODAGA)) was based on solid phase peptide synthesis protocols using the Fmoc strategy. The (68)Ga labelling protocol was optimized concerning temperature, peptide concentration and reaction time. For in vitro characterization, partition coefficient, protein binding properties, serum stability, α(v)β(3) binding affinity and cell uptake were determined. To characterize the in vivo properties, biodistribution studies and microPET imaging were carried out. For both in vitro and in vivo evaluation, α(v)β(3)-positive human melanoma M21 and α(v)β(3)-negative M21-L cells were used.RESULTS[(68)Ga]NODAGA-RGD can be produced within 5 min at room temperature with high radiochemical yield and purity (> 96%). In vitro evaluation showed high α(v)β(3) binding affinity (IC(50) = 4.7 ± 1.6 nM) and receptor-specific uptake. The radiotracer was stable in phosphate-buffered saline, pH 7.4, FeCl(3) solution, and human serum. Protein-bound activity after 180 min incubation was found to be 12-fold lower than for [(68)Ga]DOTA-RGD. Biodistribution data 60 min post-injection confirmed receptor-specific tumour accumulation. The activity concentration of [(68)Ga]NODAGA-RGD was lower than [(68)Ga]DOTA-RGD in all organs and tissues investigated, leading to an improved tumour to blood ratio ([(68)Ga]NODAGA-RGD: 11, [(68)Ga]DOTA-RGD: 4). MicroPET imaging confirmed the improved imaging properties of [(68)Ga]NODAGA-RGD compared to [(68)Ga]DOTA-RGD.CONCLUSIONThe introduced [(68)Ga]NODAGA-RGD combines easy accessibility with high stability and good imaging properties making it an interesting alternative to the (18)F-labelled RGD peptides currently used for imaging α(v)β(3) expression.

100 项与 [68Ga]NODAGA-RGD 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
颈动脉疾病	临床2期	瑞士	Centre Hospitalier Universitaire Vaudois	2012-04-01
炎症	临床2期	瑞士	Centre Hospitalier Universitaire Vaudois	2012-04-01
动脉粥样硬化斑块	临床2期	瑞士	Centre Hospitalier Universitaire Vaudois	2012-04-01