F-18-VM4-037(F-18-VM4-037) - 药物靶点：CAIX_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-VM4-037、F-18-VM4-037

靶点

CAIX

作用方式

调节剂

作用机制

CAIX调节剂(碳酸酐酶IX调节剂)

治疗领域

肿瘤泌尿生殖系统疾病消化系统疾病+ [1]

在研适应症-

非在研适应症

晚期头颈部鳞状细胞癌肝细胞癌肺癌+ [3]

原研机构

Siemens Healthineers AG

在研机构-

非在研机构

Siemens Molecular Imaging, Inc.

National Cancer Institute

权益机构-

最高研发阶段终止临床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C26H29FN6O7S2

InChIKeyQGYZPMXIVNIGKA-SZJJUGPPSA-N

CAS号1071471-25-4

关联

3

项与 F-18-VM4-037 相关的临床试验

NCT01712685

/ Terminated临床2期IIT

PET Imaging Of Renal Cell Carcinoma With 18F-VM4-037: A Phase II Pilot Study For Detection Of Disease And Correlation With VHL Mutation Status

Background:
- The drug 18F-VM4-037 is being tested for use in cancer imaging studies. It may help tumor tissue show up more clearly during scans. Researchers want to see how well it works for scans for people who have kidney cancer.
Objectives:
- To test the safety and effectiveness of 18F-VM4-037 during imaging studies of kidney cancer.
Eligibility:
- Adults at least 18 years of age with kidney cancer that will be treated with surgery.
Design:
* Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
* Participants will have two positron emission tomography (PET) scans of their kidneys. They will have the scans before and after receiving an injection of 18F-VM4-037. The scans will take about 2 hours to complete.
* About 3 weeks after the PET scans, participants will provide tumor tissue samples from their kidneys.
* This is a scanning study only. Treatment will not be provided as part of this study.

开始日期2012-10-01

申办/合作机构

National Cancer Institute

NCT00935142

/ Withdrawn临床1期IIT

Non Invasive Imaging of [18F]VM4-037 With Positron-Emission-Tomography (PET): A Phase I Trial

The purpose of this study is to determine the toxicity of the hypoxia PET-tracer [18F]-VM4-037 in cancer patients in two dose-steps:
* Step 1 (3-6 patients): a single dose of maximum 8 mCi (296 MBq) dose of [18F]VM4-037 via a bolus IV injection.
* Step 2 (3-6 patients): a single dose of maximum 12 mCi (444 MBq) dose of [18F]VM4-037 via a bolus IV injection

开始日期2012-01-01

申办/合作机构

Maastro

[+1]

NCT00884520

/ Completed早期临床1期

An Exploratory, Open Label, Multi-Center, Non-Randomized Study of [F-18]VM4-037

Phase: Exploratory Study
Objectives: To collect drug bio-distribution data, begin collection of baseline and tumor/background imaging data, acquire experience to improve study design and the conduct of future studies
Design: Exploratory, open label, nonrandomized, multi-center study
Duration: Three visits - one screening, one imaging, and one follow-up visit at 24 hours post-dose
Procedures: Informed consent, collection of demographic information and medical history, physical examinations, vital signs, 12-lead ECGs, routine blood tests to assess major organ functions, complete blood counts and clinical chemistries for safety, blood sample for CA-IX assay, pre-dose and post-dose blood samples for metabolite analysis, dosing with [F-18]VM4-037, PET imaging scan, dosimetry estimation (normals), urine collections (normals), tumor immunohistochemistry with CA-IX biomarker, follow up to imaging to collect adverse events
Subjects: Approximately sixteen (16) adult subjects including four (4) healthy volunteers and twelve (12) cancer subjects who have confirmed or highly suspected diagnosis of head & neck, lung, large solitary hepatic and renal cell cancer, as defined by protocol criteria

开始日期2009-04-01

申办/合作机构

Siemens Molecular Imaging, Inc.

100 项与 F-18-VM4-037 相关的临床结果

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100 项与 F-18-VM4-037 相关的转化医学

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100 项与 F-18-VM4-037 相关的专利（医药）

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3

项与 F-18-VM4-037 相关的文献（医药）

2016-01-01·Abdominal radiology (New York)3区 · 医学

PET/CT imaging of renal cell carcinoma with 18F-VM4-037: a phase II pilot study

3区 · 医学

Article

作者: Choyke, Peter L ; Kurdziel, Karen A ; Vocke, Cathy D ; Eclarinal, Philip ; McKinney, Yolanda L ; Linehan, W Marston ; Kwarteng, Gideon ; Anver, Miriam ; Metwalli, Adam R ; Yaqub-Ogun, Nana ; Bratslavsky, Gennady ; Adler, Stephen ; Merino, Maria J ; Lindenberg, Maria L ; Turkbey, Baris ; Weaver, Juanita ; Lin, Frank I

BACKGROUND:

Carbonic anhydrase IX (CA-IX) is a potential imaging biomarker of clear cell renal cell carcinoma (ccRCC). Here, we report the results of a phase II clinical trial of a small molecule radiotracer targeting CA-IX ((18)F-VM4-037) in ccRCC.

METHODS:

Between October 2012 and May 2013, 11 patients with kidney masses underwent (18)F-VM4-037 PET/CT prior to surgery. Dynamic imaging was performed for the first 45 min post injection and whole-body imaging was obtained at 60 min post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.

RESULTS:

All patients tolerated the radiotracer well with no adverse events. Ten of the 11 patients had histologically confirmed malignancy. One patient had a Bosniak Type 3 cyst with no tumor found at surgery. Two patients had extrarenal disease and 9 had tumors only in the kidney. Primary ccRCC lesions were difficult to visualize on PET alone due to high uptake of the tracer in the adjacent normal kidney parenchyma, however when viewed in conjunction with CT, the tumors were easily localized. Metastatic lesions were clearly visible on PET. Mean SUV for primary kidney lesions was 2.55 in all patients; in patients with histologically confirmed ccRCC, the mean SUV was 3.16. The time-activity curves (TAC) are consistent with reversible ligand binding with peak activity concentration at 8 min post injection followed by washout. Distribution Volume Ratio (DVR) of the lesions was measured using the Logan graphical analysis method. The mean DVR value across the 9 kidney lesions was 5.2 ± 2.8, (range 0.68-10.34).

CONCLUSION:

18F-VM4-037 is a well-tolerated PET agent that allows same day imaging of CA-IX expression. The agent demonstrated moderate signal uptake in primary tumors and excellent visualization of CA-IX positive metastases. While the evaluation of primary ccRCC lesions is challenging due to high background activity in the normal kidney parenchyma, 18F-VM4-037 may be most useful in the evaluation of metastatic ccRCC lesions.

2015-10-01·Molecular imaging and biology3区 · 医学

[18F]VM4-037 MicroPET Imaging and Biodistribution of Two In Vivo CAIX-Expressing Tumor Models

3区 · 医学

Article

作者: Vullo, Daniela ; Laan, Dennis ; Windhorst, Albert D ; Lieuwes, Natasja G ; Lambin, Philippe ; Mooijer, Martien ; Supuran, Claudiu T ; Eriksson, Jonas ; Dubois, Ludwig ; Peeters, Sarah G J A ; Schuit, Robert C

PURPOSE:

[(18)F]VM4-037 was recently developed as a positron emission tomography (PET) tracer for the detection of carbonic anhydrase IX (CAIX), a tumor-specific protein upregulated under hypoxic conditions. In this study, the accumulation of [(18)F]VM4-037 was determined in two CAIX-expressing preclinical human tumor models.

PROCEDURES:

U373 and HT29 tumor-bearing animals were injected with [(18)F]VM4-037 and underwent microPET imaging up to 4 h post-injection (p.i.). Biodistribution throughout the different organs was assessed at 2 and 4 h p.i. using gamma counting.

RESULTS:

MicroPET imaging showed high [(18)F]VM4-037 uptake in the abdominal region, and biodistribution revealed high radioactivity in the kidney, ileum, colon, liver, stomach, and bladder. Although high CAIX expression was confirmed in both tumor models, tumor uptake assessed with microPET and biodistribution experiments was comparable to background tissues.

CONCLUSIONS:

In this study, [(18)F]VM4-037 does not specifically accumulate in CAIX-expressing tumors, indicating that the tracer is not suitable for the detection of CAIX.

2014-10-01·Molecular imaging and biology3区 · 医学

Biodistribution and Radiation Dosimetry of the Carbonic Anhydrase IX Imaging Agent [18 F]VM4-037 Determined from PET/CT Scans in Healthy Volunteers

3区 · 医学

Article

作者: Hartmuth C. Kolb ; David Y. T. Chen ; Mohan Doss ; Joseph C. Walsh ; R. Katherine Alpaugh ; Zhihong Zhu ; Vani P. Mocharla ; Jian Q. Yu ; Michael Haka

PURPOSE:

[(18) F]VM4-037 has been developed as a positron emission tomography (PET) imaging marker to detect carbonic anhydrase IX (CA-IX) overexpression and is being investigated for use as a surrogate marker for tissue hypoxia. The purpose of this study was to determine the biodistribution and estimate the radiation dose from [(18) F]VM4-037 using whole-body PET/CT scans in healthy human volunteers.

PROCEDURES:

Successive whole-body PET/CT scans were performed after intravenous injection of [(18) F]VM4-037 in four healthy humans. The radiotracer uptakes in different organs were determined from the analysis of the PET scans. Human radiation doses were estimated using OLINDA/EXM software.

RESULTS:

High uptake of [(18) F]VM4-037 was observed in the liver and kidneys, with little clearance of activity during the study period, with mean standardized uptake values of ~35 in liver and ~22 in kidneys at ~1 h after injection. The estimated effective dose was 28 ± 1 μSv/MBq and the absorbed doses for the kidneys and liver were 273 ± 31 and 240 ± 68 μGy/MBq, respectively, for the adult male phantom. Hence, the effective dose would be 10 ± 0.5 mSv for the anticipated injected activity of 370 MBq, and the kidney and liver doses would be 101 ± 11 and 89 ± 25 mGy, respectively.

CONCLUSIONS:

[(18) F]VM4-037 displayed very high uptake in the liver and kidneys with little clearance of activity during the study period, resulting in these organs receiving the highest radiation doses among all bodily organs. Though the effective dose and the organ doses are within the limits considered as safe, the enhanced uptake of [(18) F]VM4-037 in the kidneys and liver will make the compound unsuitable for imaging overexpression of CA-IX in those two organs. However, the tracer may be suitable for imaging overexpression of CA-IX in lesions in other regions of the body such as in the lungs or head and neck region.

100 项与 F-18-VM4-037 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
肾细胞癌	临床2期	美国	National Cancer Institute	2012-10-01
晚期头颈部鳞状细胞癌	临床1期	美国	Siemens Molecular Imaging, Inc.	2009-04-01
肝细胞癌	临床1期	美国	Siemens Molecular Imaging, Inc.	2009-04-01
肺癌	临床1期	美国	Siemens Molecular Imaging, Inc.	2009-04-01
非小细胞肺癌	临床1期	美国	Siemens Molecular Imaging, Inc.	2009-04-01
鳞状细胞癌	临床1期	美国	Siemens Molecular Imaging, Inc.	2009-04-01

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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


NCT00884520 (Pubmed \| Mol Imaging Biol)	早期临床1期	-	-	[(18) F]VM4-037	製壓獵網遞鏇壓鹽觸構(淵窪願窪餘鑰鏇夢廠醖) = 簾築窪憲鑰鬱願窪獵觸夢鑰構淵積顧鹹襯齋憲 (網願範窪窪蓋艱淵廠選 ) 更多	-	2014-10-01
NCT01712685 (CTgov)	临床2期	肾细胞癌	12	PET/CT+18F-VM4-037	觸鏇構範鑰衊鬱鹽夢觸(衊糧繭繭築積膚膚積網) = 鑰膚衊鏇觸壓齋積簾窪艱壓醖鹽顧蓋鹹製膚構 (憲繭糧鏇網網窪餘艱鏇, 0.25) 更多	-	2014-09-19