BAY-94-9392(BAY-94-9392) - 药物靶点：SLC7A11_在研适应症：同种异体移植排斥反应，肺癌，多发性肺结节_专利_临床

概要

基本信息

药物类型

小分子化药、诊断用放射药物

别名

FSPG

+ [1]

靶点

SLC7A11

作用机制

SLC7A11抑制剂(胱氨酸/谷氨酸转运体抑制剂)、PET imaging(正电子发射断层成像术增强剂)

治疗领域

肿瘤免疫系统疾病呼吸系统疾病+ [3]

在研适应症

同种异体移植排斥反应肺癌多发性肺结节+ [10]

非在研适应症

晚期三阴性乳腺癌B细胞淋巴瘤3型乳腺癌+ [16]

原研机构

Piramal Pharma Limited

在研机构

Bayer AG

Asan Medical Center

National Cancer Institute

+ [4]

非在研机构

Life Molecular Imaging Ltd.GE Healthcare Holdings, Inc.

Bayer HealthCare Pharmaceuticals, Inc.

+ [1]

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

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结构

分子式C8H14FNO4

InChIKeyMKDNDKMECWBLOF-XUCPOOORSA-N

CAS号1196963-74-2

关联

14

项与 BAY-94-9392 相关的临床试验

NCT05322135 / Active, not recruiting早期临床1期IIT

A Pilot Study of Glutamine PET Imaging of Head and Neck Squamous Cell Carcinoma

We propose a focused, prospective pilot clinical imaging trial to evaluate 11C-Gln PET/CT followed by 18F-FSPG PET/CT in 20 HNSCC patients. Imaging metrics that are common to PET (e.g. SUVmax, peak or mean) will be determined.
This study will also allow the acquisition of additional safety and biodistribution data, as, to date, only a limited number of patients have been evaluated with 11C-Gln as a direct PET imaging biomarker of Gln uptake. To date, no adverse side effects have been observed. We do not anticipate any toxicity since this tracer is a naturally-occurring essential amino acid in high abundance and is administered at sub-pharmacologic doses.
A long-term goal of these preliminary studies is to validate the utility of Gln PET imaging metrics for HNSCC and to expand this imaging technique to additional patients in prospective cohorts of patients with HNSCC.

开始日期2022-09-14

申办/合作机构

The University of Texas MD Anderson Cancer Center

NCT02379377 / Recruiting临床1期IIT

PET Imaging of Hepatocellular Carcinoma With 18F-FSPG

This clinical trial studies fluorine F 18 L-glutamate derivative BAY94-9392 (18F-FSPG) positron emission tomography (PET) in imaging patients with liver cancer before undergoing surgery or transplant. Diagnostic procedures, such as 18F-FSPG PET, may help find and diagnose liver cancer and find out how far the disease has spread.

开始日期2022-02-15

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

NCT03275974 / Active, not recruiting临床1期IIT

Glutamine PET Imaging of Colorectal Cancer

The clinical trial studies how well 11C-glutamine and 18F-FSPG positron emission tomography (PET) imaging works in detecting tumors in patients with metastatic colorectal cancer compared to standard imaging methods such as magnetic resonance imaging (MRI) or computed tomography (CT) scanning.

开始日期2021-04-27

申办/合作机构

The University of Texas MD Anderson Cancer Center

100 项与 BAY-94-9392 相关的临床结果

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100 项与 BAY-94-9392 相关的转化医学

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100 项与 BAY-94-9392 相关的专利（医药）

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4

项与 BAY-94-9392 相关的文献（医药）

2013-06-01·Journal of Nuclear Medicine1区 · 医学

(S)-4-(3-¹⁸F-Fluoropropyl)-l-Glutamic Acid: An ¹⁸F-Labeled Tumor-Specific Probe for PET/CT Imaging—Dosimetry

1区 · 医学

Article

作者: Wagner, Franziska Martina ; Krause, Bernd Joachim ; Hultsch, Christina ; Smolarz, Kamilla ; Sparks, Richard B. ; Graner, Frank-Philipp ; Bacher-Stier, Claudia ; Dinkelborg, Ludger M. ; Fels, Lueder ; Ramsay, Susan ; Schwaiger, Markus

The glutamic acid derivative (S)-4-(3-(18)F-Fluoropropyl)-l-glutamic acid ((18)F-FSPG, alias BAY 94-9392), a new PET tracer for the detection of malignant diseases, displayed promising results in non-small cell lung cancer patients. The aim of this study was to provide dosimetry estimates for (18)F-FSPG based on human whole-body PET/CT measurements.METHODS(18)F-FSPG was prepared by a fully automated 2-step procedure and purified by a solid-phase extraction method. PET/CT scans were obtained for 5 healthy volunteers (mean age, 59 y; age range, 51-64 y; 2 men, 3 women). Human subjects were imaged for up to 240 min using a PET/CT scanner after intravenous injection of 299 ± 22.5 MBq of (18)F-FSPG. Image quantification, time-activity data modeling, estimation of normalized number of disintegrations, and production of dosimetry estimates were performed using the RADAR (RAdiation Dose Assessment Resource) method for internal dosimetry and in general concordance with the methodology and principles as presented in the MIRD 16 document.RESULTSBecause of the renal excretion of the tracer, the absorbed dose was highest in the urinary bladder wall and kidneys, followed by the pancreas and uterus. The individual organ doses (mSv/MBq) were 0.40 ± 0.058 for the urinary bladder wall, 0.11 ± 0.011 for the kidneys, 0.077 ± 0.020 for the pancreas, and 0.030 ± 0.0034 for the uterus. The calculated effective dose was 0.032 ± 0.0034 mSv/MBq. Absorbed dose to the bladder and the effective dose can be reduced significantly by frequent bladder-voiding intervals. For a 0.75-h voiding interval, the bladder dose was reduced to 0.10 ± 0.012 mSv/MBq, and the effective dose was reduced to 0.015 ± 0.0010 mSv/MBq.CONCLUSIONOn the basis of the distribution and biokinetic data, the determined radiation dose for (18)F-FSPG was calculated to be 9.5 ± 1.0 mSv at a patient dose of 300 MBq, which is of similar magnitude to that of (18)F-FDG (5.7 mSv). The effective dose can be reduced to 4.5 ± 0.30 mSv (at 300 MBq), with a bladder-voiding interval of 0.75 h.

2012-10-01·Clinical Cancer Research1区 · 医学

Exploratory Clinical Trial of (4S)-4-(3-[18F]fluoropropyl)-l-glutamate for Imaging xC− Transporter Using Positron Emission Tomography in Patients with Non–Small Cell Lung or Breast Cancer

1区 · 医学

Article

作者: Gong, Gyungyub ; Lee, Jong Won ; Gambhir, Sanjiv S. ; Dinkelborg, Ludger M. ; Choi, Chang-Min ; Hultsch, Christina ; Baek, Sora ; Bacher-Stier, Claudia ; Fels, Lüder ; Oh, Seung Jun ; Koglin, Norman ; Mittra, Erik S. ; Schatz, Christoph A. ; Ryu, Jin-Sook ; Moon, Dae Hyuk ; Ahn, Sei Hyun

AbstractPurpose: (4S)-4-(3-[18F]fluoropropyl)-l-glutamate (BAY 94-9392, alias [18F]FSPG) is a new tracer to image xC− transporter activity with positron emission tomography (PET). We aimed to explore the tumor detection rate of [18F]FSPG in patients relative to 2-[18F]fluoro-2-deoxyglucose ([18F]FDG). The correlation of [18F]FSPG uptake with immunohistochemical expression of xC− transporter and CD44, which stabilizes the xCT subunit of system xC−, was also analyzed.Experimental Design: Patients with non–small cell lung cancer (NSCLC, n = 10) or breast cancer (n = 5) who had a positive [18F]FDG uptake were included in this exploratory study. PET images were acquired following injection of approximately 300 MBq [18F]FSPG. Immunohistochemistry was done using xCT- and CD44-specific antibody.Results: [18F]FSPG PET showed high uptake in the kidney and pancreas with rapid blood clearance. [18F]FSPG identified all 10 NSCLC and three of the five breast cancer lesions that were confirmed by pathology. [18F]FSPG detected 59 of 67 (88%) [18F]FDG lesions in NSCLC, and 30 of 73 (41%) in breast cancer. Seven lesions were additionally detected only on [18F]FSPG in NSCLC. The tumor-to-blood pool standardized uptake value (SUV) ratio was not significantly different from that of [18F]FDG in NSCLC; however, in breast cancer, it was significantly lower (P < 0.05). The maximum SUV of [18F]FSPG correlated significantly with the intensity of immunohistochemical staining of xC− transporter and CD44 (P < 0.01).Conclusions: [18F]FSPG seems to be a promising tracer with a relatively high cancer detection rate in patients with NSCLC. [18F]FSPG PET may assess xC− transporter activity in patients with cancer. Clin Cancer Res; 18(19); 5427–37. ©2012 AACR.

2011-09-15·Clinical Cancer Research1区 · 医学

Specific PET Imaging of xC− Transporter Activity Using a 18F-Labeled Glutamate Derivative Reveals a Dominant Pathway in Tumor Metabolism

1区 · 医学

Article

作者: Berndt, Mathias ; Gekeler, Volker ; Schmitt-Willich, Heribert ; Stephens, Andrew W. ; Mueller, Andre ; Dinkelborg, Ludger M. ; Friebe, Matthias ; Toschi, Luisella ; Koglin, Norman

AbstractPurpose: 18F-labeled small molecules targeting adaptations of tumor metabolism possess the potential for early tumor detection with high sensitivity and specificity by positron emission tomography (PET) imaging. Compounds tracing deranged pathways other than glycolysis may have advantages in situations where 2-[18F]fluoro-2-deoxy-d-glucose (FDG) has limitations. The aim of this study was the generation of a metabolically stable 18F-labeled glutamate analogue for PET imaging of tumors.Experimental Design: Derivatives of l-glutamate were investigated in cell competition assays to characterize the responsible transporter. An automated radiosynthesis was established for the most promising candidate. The resulting 18F-labeled PET tracer was characterized in a panel of in vitro and in vivo tumor models. Tumor specificity was investigated in the turpentine oil-induced inflammation model in rats.Results: A fluoropropyl substituted glutamate derivative showed strong inhibition in cell uptake assays. The radiosynthesis was established for (4S)-4-(3-[18F]fluoropropyl)-l-glutamate (BAY 94-9392). Tracer uptake studies and analysis of knockdown cells showed specific transport of BAY 94-9392 via the cystine/glutamate exchanger designated as system xC−. No metabolites were observed in mouse blood and tumor cells. PET imaging with excellent tumor visualization and high tumor to background ratios was achieved in preclinical tumor models. In addition, BAY 94-9392 did not accumulate in inflammatory lesions in contrast to FDG.Conclusions: BAY 94-9392 is a new tumor-specific PET tracer which could be useful to examine system xC− activity in vivo as a possible hallmark of tumor oxidative stress. Both preclinical and clinical studies are in progress for further characterization. Clin Cancer Res; 17(18); 6000–11. ©2011 AACR.

100 项与 BAY-94-9392 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15041

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
晚期三阴性乳腺癌	临床前	美国	National Cancer Institute	2015-07-01
B细胞淋巴瘤	临床前	美国	National Cancer Institute	2015-07-01
3型乳腺癌	临床前	美国	National Cancer Institute	2015-07-01
间皮瘤	临床前	美国	National Cancer Institute	2015-07-01
转移性肾细胞癌	临床前	美国	National Cancer Institute	2015-07-01
非小细胞肺癌IIIA期	临床前	美国	National Cancer Institute	2015-07-01
非小细胞肺癌IIIB期	临床前	美国	National Cancer Institute	2015-07-01
多发性肺结节	临床前	美国	National Cancer Institute	2015-06-16
尼古丁成瘾	临床前	美国	National Cancer Institute	2015-06-16
孤立性肺结节	临床前	美国	National Cancer Institute	2015-06-16

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02448225 (CTgov)	临床2期	肺癌 \| 尼古丁成瘾 \| 孤立性肺结节 \| 多发性肺结节	46	fluorodeoxyglucose F-18+Fluorine F 18 L-glutamate Derivative BAY94-9392	夢憲蓋醖鹹糧願醖構範(鹽醖鹽糧鹹網憲願選鹹) = 繭顧艱淵憲築壓鬱繭膚範選製範鹹積艱鹽鏇積 (製鏇襯築餘觸網膚鹹窪, 繭簾積積夢憲選範鹹廠 ~ 築選襯觸鑰蓋糧窪夢獵) 更多	-	2022-05-10
NCT02599194 (CTgov)	临床2期	转移性肾细胞癌 \| 非小细胞肺癌IIIA期 \| 间皮瘤 \| B细胞淋巴瘤 \| 非小细胞肺癌IIIB期 \| 转移性乳腺癌 \| 转移性非小细胞肺癌 \| 晚期三阴性乳腺癌 \| 3型乳腺癌	7	18F-FDG+18F-FSPG	鑰壓鏇構憲窪簾鏇襯鹹(膚膚襯鏇構顧窪製鹽繭) = 鏇網齋餘觸鏇糧繭構簾壓憲衊簾鏇膚鑰壓鹹膚 (簾鹽襯膚鏇顧襯艱鏇願, 鬱簾繭艱鏇構蓋鏇鑰獵 ~ 鑰淵膚壓醖範窪糧膚願) 更多	-	2019-01-03
AACR2012	N/A	肿瘤	-	FSPG (BAY 94-9392)	鹹廠醖淵繭艱製遞醖積(觸衊繭願積襯艱築蓋獵) = significant correlation between FSPG uptake and protein expression of both the xCT subunit and CD44 艱簾艱獵製遞衊繭鏇淵 (鏇廠齋鬱獵觸構齋齋鹹 )	-	2012-04-15