Delving into the Latest Updates on F-18-VM4-037 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Diagnostic radiopharmaceuticals

Synonyms

18F-VM4-037, F-18-VM4-037

Target

CAIX

Action

modulators

Mechanism

CAIX modulators(Carbonic anhydrase IX modulators)

Therapeutic Areas

NeoplasmsUrogenital DiseasesDigestive System Disorders+ [1]

Active Indication-

Inactive Indication

Advanced Head and Neck Squamous Cell CarcinomaHepatocellular CarcinomaLung Cancer+ [3]

Originator Organization

Siemens Healthineers AG

Active Organization-

Inactive Organization

Siemens Molecular Imaging, Inc.

National Cancer Institute

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC26H29FN6O7S2

InChIKeyQGYZPMXIVNIGKA-SZJJUGPPSA-N

CAS Registry1071471-25-4

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.

Start Date01 Oct 2012

Sponsor / Collaborator

National Cancer Institute

NCT00935142

/ WithdrawnPhase 1IIT

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

Start Date01 Jan 2012

Sponsor / Collaborator

Maastro

[+1]

NCT00884520

/ CompletedEarly Phase 1

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

Start Date01 Apr 2009

Sponsor / Collaborator

Siemens Molecular Imaging, Inc.

100 Clinical Results associated with F-18-VM4-037

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100 Translational Medicine associated with F-18-VM4-037

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100 Patents (Medical) associated with F-18-VM4-037

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3

Literatures (Medical) associated with F-18-VM4-037

01 Jan 2016·Abdominal radiology (New York)Q3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: Choyke, Peter L ; Kurdziel, Karen A ; Vocke, Cathy D ; Eclarinal, Philip ; McKinney, Yolanda L ; Linehan, W Marston ; Kwarteng, Gideon ; Metwalli, Adam R ; Anver, Miriam ; 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.

01 Oct 2015·Molecular imaging and biologyQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: Vullo, Daniela ; Laan, Dennis ; Windhorst, Albert D ; Mooijer, Martien ; Lieuwes, Natasja G ; Lambin, Philippe ; 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.

01 Oct 2014·Molecular imaging and biologyQ3 · MEDICINE

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

Q3 · MEDICINE

Article

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

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 Deals associated with F-18-VM4-037

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Renal Cell Carcinoma	Phase 2	United States	National Cancer Institute	01 Oct 2012
Advanced Head and Neck Squamous Cell Carcinoma	Phase 1	United States	Siemens Molecular Imaging, Inc.	01 Apr 2009
Hepatocellular Carcinoma	Phase 1	United States	Siemens Molecular Imaging, Inc.	01 Apr 2009
Lung Cancer	Phase 1	United States	Siemens Molecular Imaging, Inc.	01 Apr 2009
Non-Small Cell Lung Cancer	Phase 1	United States	Siemens Molecular Imaging, Inc.	01 Apr 2009
Squamous Cell Carcinoma	Phase 1	United States	Siemens Molecular Imaging, Inc.	01 Apr 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00884520 (Pubmed \| Mol Imaging Biol)	Early Phase 1	-	-	[(18) F]VM4-037	sfsvysejcm(vajilkzfrw) = lsouvmwcwy xqtfcwihtf (uupmkbwxcl ) View more	-	01 Oct 2014
NCT01712685 (CTgov)	Phase 2	Renal Cell Carcinoma	12	PET/CT+18F-VM4-037	ywydbxaeds(kzqwjgwxbi) = ssbgwlnmlp ymmnaxenwc (rlrxldodhn, 0.25) View more	-	19 Sep 2014