[18F]DCFBC([18F]DCFBC) - 药物靶点：PSMA_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

18F DCFBC

靶点

PSMA

作用方式

抑制剂

作用机制

PSMA抑制剂(前列腺癌特异性膜抗原抑制剂)

治疗领域

肿瘤泌尿生殖系统疾病

在研适应症-

非在研适应症

晚期前列腺癌转移性前列腺癌

原研机构

Washington University in St. Louis

在研机构-

非在研机构

The Sidney Kimmel Comprehensive Cancer Center

权益机构-

最高研发阶段无进展临床1/2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C16H19FN2O7S

InChIKeyIDTMSHGCAZPVLC-STUNTBJNSA-N

CAS号1169942-33-9

关联

4

项与 [18F]DCFBC 相关的临床试验

NCT02190279

/ Completed早期临床1期IIT

A Pilot Study of 18F-DCFBC PET/CT in Prostate Cancer

Background:
- Prostate cancer is the second leading cause of cancer deaths in American men. A chemical called a radiotracer helps doctors get images of this type of cancer. Researchers want to test a radiotracer called N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-(18)F-fluorobenzyl-L-cysteine ((18)F-DCFBC) (18F-DCFBC).
Objective:
- To see if the radiotracer 18F-DCFBC can identify sites of prostate cancer in the body.
Eligibility:
- Men ages 18 and over with prostate cancer. The cancer must be newly diagnosed, have relapsed, or has spread outside the prostate.
Design:
* Participants will be screened with physical exam and medical history. They will give a blood sample.
* Participants will be divided into three groups.
Group 1: people with cancer only in the prostate scheduled for surgical prostate removal or biopsy at National Institutes of Health (NIH).
Group 2: people who had their prostate removed or had radiation therapy and now have a rising prostate-specific antigen (PSA) without other signs of disease.
Group 3: people whose cancer has spread to other areas of the body.
* Participants will have 18F-DCFBC injected into a vein then imaged in a positron emission tomography (PET)/computed tomography (CT) camera. During the scans, they will lie on their back on the scanner table.
* Group 1 will have a magnetic resonance imaging (MRI) scan. A tube will be placed in the rectum. Coils may be wrapped around the outside of the pelvis. Participants will have a contrast agent injected through an intravenous line.
* Group 3 will have another PET/CT scan with a different radiotracer, 18F NaF, within 21 days of the 18F-DCFBC scan to look for prostate cancer in the bone.
* Group 3 will repeat the two PET/CT scans 4-6 months after the initial scans.
* A few days after each scan, participants will be contacted for follow-up.

开始日期2014-07-12

申办/合作机构

National Cancer Institute

NCT01815515

/ Completed临床1/2期IIT

Evaluation of 18F-DCFBC PSMA-based PET Imaging for Detection of Metastatic Prostate Cancer.

This research is being done to see if an investigational radioactive drug called 18F-DCFBC can help us find cancer that has spread (metastatic disease) from its original site in people who have cancer in their prostate to other parts of their body.

开始日期2013-03-01

申办/合作机构

The Sidney Kimmel Comprehensive Cancer Center

NCT01496157

/ Completed临床1/2期IIT

Evaluation of PSMA-based PET as an Imaging Biomarker of Primary Prostate Cancer

The objective of this study is to evaluate a radiolabeled urea-based small molecule inhibitor of prostate-specific membrane antigen (PSMA), [18F]DCFBC (DCFBC), as a PET imaging biomarker of prostate cancer detection and aggressiveness at initial diagnosis. PSMA is a well characterized histological marker of prostate cancer tumor aggressiveness but a quantitative non-invasive method for PSMA detection and monitoring is not currently available. Development of such an imaging biomarker would be useful to differentiate indolent from aggressive prostate cancer phenotypes and allow for selection of appropriate risk adaptive therapies. The investigators preliminary first-in-human studies demonstrate high specific DCFBC uptake in metastatic prostate cancer and feasibility for prostate cancer imaging. The investigators propose to study patients initially diagnosed with biopsy-positive prostate cancer to determine if DCFBC uptake and location by PET imaging will be positively correlated with prostate cancer by prostatectomy tissue step-section analysis. DCFBC uptake at sites of suspected metastatic disease will be compared to conventional imaging modalities (CT, bone scan) and biopsy results when available. In addition, DCFBC-PET uptake quantification will be compared with expression levels of PSMA and other prostate cancer relevant markers (PSA, Ki-67, TMPRSS2-ERG) by prostate tissue immunohistochemistry analysis and compared with clinical prognostic markers (PSA, Gleason score, clinical stage, Partin tables derived prediction of pathologic stage).

开始日期2012-09-11

申办/合作机构

The Sidney Kimmel Comprehensive Cancer Center

100 项与 [18F]DCFBC 相关的临床结果

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100 项与 [18F]DCFBC 相关的转化医学

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100 项与 [18F]DCFBC 相关的专利（医药）

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4

项与 [18F]DCFBC 相关的文献（医药）

2019-09-06·ACS Catalysis

Electrostatic Effects Accelerate Decatungstate-Catalyzed C–H Fluorination Using [¹⁸F]- and [¹⁹F]NFSI in Small Molecules and Peptide Mimics

作者: Martin, Rainer E. ; Warren, Jeffrey J. ; Yuan, Zheliang ; Yang, Hua ; Britton, Robert ; Weber, David S. ; Malik, Noeen ; Schaffer, Paul ; Čolović, Milena ; Wilson, Darryl ; Bénard, François

The site-selective fluorination of unactivated C(sp³)-H bonds provides unique opportunities to rapidly alter drug properties or generate radiotracers for positron emission tomog. (PET) imaging.Toward this goal, photoactivated decatungstate (DT) is capable of generating carbon radicals through hydrogen atom transfer that subsequently undergo fluorination by reaction with N-fluorobenzenesulfonimide (NFSI) or [¹⁸F]NFSI.This process enables C(sp³)-H fluorination of a wide range of aliphatic compounds, though reaction rates can be highly variable and limit applications in radiotracer synthesis.Here, we demonstrate that cationic ammonium functions in aliphatic mols. promote formation of a precursor complex with DT that significantly increases the rate of C-H abstraction.The general utility of this rate-accelerating electrostatic effect is demonstrated on more than 30 ammonium-containing mols., including amino acids, heterocycles, and pseudopeptides.Moreover, this effect is highlighted in the rapid production of [¹⁸F]Glu-U-FHLeu, a ¹⁸F-labeled prostate specific membrane antigen (PSMA)-binding ligand.

2017-10-01·Clinical nuclear medicine3区 · 医学

18F-DCFBC Prostate-Specific Membrane Antigen–Targeted PET/CT Imaging in Localized Prostate Cancer

3区 · 医学

Article

作者: McKinney, Yolanda ; Bhattacharyya, Sibaprasad ; Choyke, Peter L ; Eclarinal, Philip ; Berman, Rose ; Bednarova, Sandra ; Mease, Ronnie C ; Ton, Anita T ; Pinto, Peter A ; Hill, Craig ; Jacobs, Paula M ; Pomper, Martin G ; Wood, Bradford J ; Adler, Stephen ; Mena, Esther ; Merino, Maria J ; Turkbey, Baris ; Lindenberg, Liza ; Afari, George

PURPOSE:

To assess the ability of (N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-F-fluorobenzyl-L-cysteine) (F-DCFBC), a prostate-specific membrane antigen-targeted PET agent, to detect localized prostate cancer lesions in correlation with multiparametric MRI (mpMRI) and histopathology.

METHODS:

This Health Insurance Portability and Accountability Act of 1996-compliant, prospective, institutional review board-approved study included 13 evaluable patients with localized prostate cancer (median age, 62.8 years [range, 51-74 years]; median prostate-specific antigen, 37.5 ng/dL [range, 3.26-216 ng/dL]). Patients underwent mpMRI and F-DCFBC PET/CT within a 3 months' window. Lesions seen on mpMRI were biopsied under transrectal ultrasound/MRI fusion-guided biopsy, or a radical prostatectomy was performed. F-DCFBC PET/CT and mpMRI were evaluated blinded and separately for tumor detection on a lesion basis. For PET image analysis, MRI and F-DCFBC PET images were fused by using software registration; imaging findings were correlated with histology, and uptake of F-DCFBC in tumors was compared with uptake in benign prostatic hyperplasia nodules and normal peripheral zone tissue using the 80% threshold SUVmax.

RESULTS:

A total of 25 tumor foci (mean size, 1.8 cm; median size, 1.5 cm; range, 0.6-4.7 cm) were histopathologically identified in 13 patients. Sensitivity rates of F-DCFBC PET/CT and mpMRI were 36% and 96%, respectively, for all tumors. For index lesions, the largest tumor with highest Gleason score, sensitivity rates of F-DCFBC PET/CT and mpMRI were 61.5% and 92%, respectively. The average SUVmax for primary prostate cancer was higher (5.8 ± 4.4) than that of benign prostatic hyperplasia nodules (2.1 ± 0.3) or that of normal prostate tissue (2.1 ± 0.4) at 1 hour postinjection (P = 0.0033).

CONCLUSIONS:

The majority of index prostate cancers are detected with F-DCFBC PET/CT, and this may be a prognostic indicator based on uptake and staging. However, for detecting prostate cancer with high sensitivity, it is important to combine prostate-specific membrane antigen PET/CT with mpMRI.

2012-11-26·Journal of medicinal chemistry1区 · 医学

Radiofluorinated Derivatives of 2-(Phosphonomethyl)pentanedioic Acid as Inhibitors of Prostate Specific Membrane Antigen (PSMA) for the Imaging of Prostate Cancer

1区 · 医学

Article

作者: Graham, Keith ; Dinkelborg, Ludger ; Schäfer, Martina ; Gromov, Alexey V. ; Kettschau, Georg ; Hassfeld, Jorma ; Lesche, Ralf ; Böhnke, Niels

For prostate cancer, prostate specific membrane antigen (PSMA) has been identified as a diagnostic and therapeutic target. Fluorinated derivatives of 2-(phosphonomethyl)pentanedioic acid were designed and synthesized to explore whether this fluorine-substituent is tolerated in the pentanedioic acid moiety that is common to almost all PSMA targeting small molecule inhibitors. The binding affinities of the racemic and individual stereoisomers of 2-fluoro-4-(phosphonomethyl)pentanedioic acid were determined and showed that the introduction of fluorine was well tolerated. The radiosynthesis of the analogous 2-[(18)F]fluoro-4-(phosphonomethyl)pentanedioic acid was developed and evaluated in vivo with the PSMA positive LNCaP human prostate cancer cell. The biological results demonstrated specific binding of the tracer to PSMA positive tumors in mice. These results warrant the further evaluation of this class of compounds as radiolabeled tracers for the detection and staging of prostate cancer.

100 项与 [18F]DCFBC 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14772

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
转移性前列腺癌	临床2期	美国	The Sidney Kimmel Comprehensive Cancer Center	2013-03-01
晚期前列腺癌	临床1期	美国	The Sidney Kimmel Comprehensive Cancer Center	2010-09-01

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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


NCT02190279 (CTgov)	早期临床1期	前列腺癌	116	18F DCFBC (Suspected Localized Prostate Cancer)	壓齋淵遞艱製窪製夢衊 = 鑰範積艱鏇選膚網窪襯壓鏇憲遞製蓋糧構衊壓 (獵願艱醖積遞積淵廠鏇, 糧廠簾窪鹽鑰鏇淵衊鬱 ~ 醖遞餘艱願簾構範範選) 更多	-	2019-04-23
NCT02190279 (CTgov)	早期临床1期	前列腺癌	116	18F DCFBC (Biochemical Recurrence)	壓齋淵遞艱製窪製夢衊 = 積鑰鑰夢壓鏇淵憲蓋積壓鏇憲遞製蓋糧構衊壓 (獵願艱醖積遞積淵廠鏇, 製夢繭鑰遞遞顧範鬱蓋 ~ 艱夢鹽壓鹹蓋範膚繭範) 更多	-	2019-04-23
NCT01496157 (CTgov)	临床1/2期	前列腺癌	15	18F-DCFBC	製憲艱窪醖築顧憲廠襯 = 淵積夢築廠選構襯簾鬱衊鹽壓壓範壓築醖製網 (觸衊廠窪範窪齋廠憲願, 壓衊繭網廠襯鏇遞願鏇 ~ 顧願顧鑰膚鬱鹽觸淵鏇) 更多	-	2018-08-28
NCT01815515 (CTgov)	临床1/2期	转移性前列腺癌	22	18F-DCFBC	觸襯廠鏇製艱齋鑰願衊 = 淵蓋獵願醖簾獵築獵鏇製憲夢選夢範繭夢衊鹹 (築膚鬱繭醖築獵簾襯艱, 選獵願鏇鑰艱衊醖淵膚 ~ 範糧構鏇憲膚艱觸醖繭) 更多	-	2018-08-20
NCT02190279 (Pubmed \| Clin Nucl Med)	早期临床1期	局限性前列腺癌	13	18F-DCFBC (F-DCFBC PET/CT)	餘餘觸範淵積繭繭膚衊(範壓鹽範壓鑰糧鬱蓋鹹) = 鑰醖膚製窪鹽襯鹹觸觸鏇遞遞鏇醖鏇齋壓願餘 (鏇積襯網製襯夢醖蓋願 ) 更多	-	2017-10-01
NCT02190279 (Pubmed \| Clin Nucl Med)	早期临床1期	局限性前列腺癌	13	18F-DCFBC (mpMRI)	餘餘觸範淵積繭繭膚衊(範壓鹽範壓鑰糧鬱蓋鹹) = 鬱獵鏇餘襯範顧觸淵繭鏇遞遞鏇醖鏇齋壓願餘 (鏇積襯網製襯夢醖蓋願 ) 更多	-	2017-10-01