How important is true quantification to your in vivo imaging results?

How important is
true quantification
to your in vivo imaging results?
True quantification to the picomole
with FMT 3D in vivo imaging...
because biology doesn’t
happen in two dimensions.
Cardiovascular
Pulmonary
The FMT 2500 LX quantitative tomography system with VisEn’s suite
of fluorescent agents provides the leading fluorescence tomographic
imaging solution for true quantification of deep tissue targets in vivo.
Using one or multiple of VisEn’s targeted, activatable and vascular
agents and labels (for multiplexed results), a researcher can quantify
a broad range of biologic targets, pathways and processes in vivo. In
addition, the FMT is specifically developed for robust multi-modality
imaging, allowing for the easy fusion of FMT with PET, MRI, CT and
SPECT data sets. Whether you are imaging a particular biomarker,
disease pathway or monitoring therapeutic efficacy, the FMT is easy
to learn, fast to incorporate into a high-throughput workflow and
quickly produces unmatched results.
CNS
Oncology
Bone and
Skeletal Disease
Inflammation
Infectious Disease
Infected
2D Planar
0.30 0.34
Co-registered FMT-MRI imaging
data of proteolytic activities
validating splenic deployment of
monocytes to the heart following
myocardial infarction.*
0.38
counts/energy 3D FMT
0.41 0.45 100 325
550
nM
775 1000
Eosinophil cathepsin activity
quantified with FMT and ProSense
in an ovalbumin-induced asthma
model (right); not visible with planar
fluorescence (left).
300
350
400
450
FMT tomographic imaging in
brain for EAE disease severity.
Quantification of AngioSense.
nM
500
2D Planar
0.01
counts/energy 3D FMT
1.0 50
FMT quantitative
cancer metastasis
ProSense (right);
planar fluorescence
nM
2000
imaging of breast
to the lung, using not visible with (left).
Control Mouse
100 375
650
nM
925 1200
CAIA Mouse
100 375
650
nM
925 1200
FMT quantitative imaging of arthritis
using ProSense to quantify arthritic
inflammation in vivo in CAIA mice.
Side View
0.00
943.85
Front View
1887.70
2831.55
nM
3775.39
FMT quantification of acute
edema and cellular inflammatory
response. Quantification of
AngioSense.
0.00
211.32
422.64
633.95
nM
845.25
FMT quantitative imaging of
Schistosomiasis using ProSense
showing infection of liver and lower
gastrointestinal tract.
*Image courtesy of Swirski et al, Science,
31 July 2009 Vol 325, pp. 612
2
VISEN MEDICAL // OVERVIEW OF APPLICATIONS
3
FMT =
3D Quantitative Fluorescence Results
of Deep Tissue Molecular Targets
™
Quantification of VisEn
VivoTag agent in a
Lymphoma Model
showing lymph nodes
and lung metastasis
Quantified with
the FMT 2500™ to
the Picomole by:
nM
2205.18
1880.67
1556.17
1231.66
1907.15
Based on our proprietary FMT (Fluorescence Molecular Tomography)
technology, the FMT 2500 LX in vivo imaging system provides
non-invasive, whole body, deep tissue quantitative in vivo imaging
for preclinical applications.
™
True quantification to the
picomole with FMT 3D
in vivo imaging and agents….
…because biology doesn’t
happen in two dimensions.
™
•
•
•
•
•
•
•
Easily and efficiently obtain quantitative data in your animal models of disease
Measure and monitor multiple biological processes simultaneously
Generate 3D, information-rich results
Integrate FMT in vivo data with in vitro readouts from microscopy and cell-based imaging
Co-register data with CT, SPECT, PET or MR images
Use Reflectance mode for baseline comparison
Use Quantitative Tomography mode for data quantification and 3D image generation
Quantitative Tomography combined with VisEn’s suite of
fluorescent in vivo imaging agents and dyes enables scientists to:
•
•
•
•
•
•
4
VISEN MEDICAL // OVERVIEW OF APPLICATIONS
Measure, monitor and quantify biological targets, processes and pathways in vivo
Deepen their understanding of disease mechanisms, disease progression and therapeutic responses
Use tomographic reconstructions to generate data sets from defined ROIs within the subject
Obtain functional and biological data to enhance data and decision-making in research
and drug development projects
Monitor disease progression and therapeutic response in longitudinal studies
Integrate in vitro and in vivo data sets from profiling through translational research
VISEN MEDICAL // OVERVIEW
5
Quick to learn.
Fast to image.
Easy to quantify.
FMT for True Quantification:
3 Steps to Generate Quantitative
Tomographic Data In Vivo
STEP 1 // FMT Data Generation
x
•
•
Transillumination: FMT transillumination of animal using powerful 80 mW lasers.
Creating Baseline Absorption Profiles: Baseline absorption profiles of each
mouse’s biological composition are measured by a laser-light raster scan. Paired
absorption and fluorescence data maps generated from 10,000 – 100,000 source
detector laser projections.
y
CCD
Camera
Lens
Filter
Wheel
Mouse
Immobilized in
Imaging Cassette
Mouse (to scale)
Laser
Scanning:
2 - 4 Distinct
Lasers
(80mW
NIR laser)
X-Y Stage
FMT laser-driven transillumination generates
paired absorption and fluorescence data
maps throughout the animal
Fiducial wells for co-registration
with other modules
The anesthetized mouse is comfortably placed in VisEn’s portable Animal Imaging Cassette. Imaging sessions
are rapid (2-3 minutes per animal), animal handling is simple and the mouse remains stable and immobilized for
consistent, repetitive imaging results.
STEP 2 // FMT Normalization
•
•
•
Normalized fluorescence measurements generated by processing all
paired absorption and fluorescence acquisition data.
FMT minimizes the distorting effects of in vivo tissue heterogeneity, taking into
account surface boundaries, tissue spectral characteristics and wave-guiding
effects to correct and normalize each fluorescent measurement.
Data normalized by FMT algorithmic models of photon transport in tissue.
A
A. Scan field
B
B. Excitation
scan image
C
C. Fluorescence
scan image
Inserting the Animal Imaging
Cassette into the FMT 2500
Easily position the anesthetized animal in the Imaging Cassette within
the heated imaging chamber. Gas anesthesia is maintained.
STEP 3 // FMT Reconstruction
•
•
•
•
•
•
6
Fluorescence quantified to the picomole at each point in the subject including
deep tissue targets
Fluorescence measurements calculated throughout the user-selected regions
of Interest (ROI)
Data provided in universal formats for analysis (including DICOM), database
building, and decision-making
Easily create animated movies including dynamic presentation of quantification
data for presentation
Data and images easily exported for multi-modality image fusion
Quantification is performed on all animals at any depth with equal accuracy and
without the need for an artificial image atlas for referential quantification.
VISEN MEDICAL // OVERVIEW OF APPLICATIONS
3D ROI analysis measuring protease activity in the lungs
Easy Experiment Set-Up
Quick Tomographic Scan
Quantitative Analysis
VISEN MEDICAL // FMT WORKFLOW
7
Multi-Modality Imaging:
Simple Image Fusion,
Powerful In Vivo Results
STEP Anesthetize Animal in Imaging Cassette
1
Because one modality does not answer all
biological questions, the FMT has been designed
to easily integrate its molecular tomographic data
with other functional and anatomical modalities
like CT, MRI, SPECT and PET. One can therefore
best leverage a core facility’s instrumentation and
investments to gather more robust, multi-variant
biological insights using the FMT.
Animals are anesthetized and secured in the
Animal Cassette for imaging. Fiducial markers on
the side of the Cassette allow for co-registration
using FMT and a secondary modality.
STEP Select a Multi-Modality Adaptor
2
Bruker MRI
Multi-Modality Adaptor
Gamma Medica CT
Multi-Modality Adaptor
Siemens Inveon CT/PET/SPECT
Multi-Modality Adaptor
Quantified In Vivo Readouts of Disease
Progression and Therapeutic Response
Angiogenesis
Arthritis
Asthma and COPD
Biodistribution
Bone Remodeling
Cardiology
CNS Disorders
Drug Development
Fibrosis
Infectious Disease
Inflammation
Neurobiology
Oncology
Respiratory Disease
Skeletal Disease
Stem Cell
Toxicology
Vascular Biology
The FMT imaging system is perfect
for quantifying a broad range of
in vivo imaging biomarkers, disease
pathways and therapeutic response
levels. As an integrated part of
any research facility focusing on a
single application area, or for a core
imaging facility serving multiple
departments, the FMT is quickly
learned, fast to implement and easily
provides quantifiable, insightful data.
GE CT
Multi-Modality Adaptor
VisEn has 4 models of its Multi-Modality Adaptor available for imaging with CT, MRI, SPECT and PET.
STEP
STEP
3
4
The Animal Cassette is then placed inside the MultiModality Adaptor. The animal remains immobilized
for easy multi-modality imaging.
ProSense750
Size: 170 voxels, 172.9 mm3 (9-307-19 10-14)
Threshold: 80.0 nM
Min: 80.1 nM Max: 277.22 nM
Mean: 138.51 nM StdDev: 47.94 nM
Total: 23.94 pmol
The Multi-Modality Adaptor is placed in the second
modality and the animal is imaged. The fiducial
markers allow for easy alignment of images between
the two modalities.
ProSense750 4T1 Co-Reg: 2-2
30.00
45.01
60.02
75.03
nM
90.04
MMPSense680 4T1 Co-Reg: 2-1
19.75
41.27
62.79
84.31
nM
105.84
Multiplexed quantification of MMPs
and cathepsins in 4T1 mammary
fat pad tumors. Quantification of
ProSense 750 (red) and MMPSense
680 (green).
Lung Metastasis
Size: 87 voxels, 86.0 mm3
Threshold: 250.0 nM
Min: 251.55 nM Max: 1097.0 nM
Mean: 436.08 nM
Total: 37.52 pmol
AngioSense 680
Size: 358 voxels, 346.9 mm3
Min: 10.03 nM Max: 33.42 nM
Mean: 18.37 nM
Total: 6.37 pmol
AngioSense680 #3 Brain Tumor 1:1-1
10.00
17.50
25.00
32.50
nM
40.00
VivoTag-S750-conjugate
250.00
437.50
625.00
812.50
nM
1000.00
Quantification of AngioSense 680 for Quantification of VivoTag 750 in a
tumor vascularity in model of brain
model of lung metastasis.
glioblastoma.
Lymph Nodes
FMT Slices
STEP Generation of Fused Multi-Modality Images and Data Sets
5
Ovarian Tumor Model
Quantification: 14.2 pmol
ProSense Fluorescence
Volume: 163 mm3
MRI
8
FMT
MRI-FMT
Fusion Image
Multi-modality FMT – CT
imaging of atherosclerotic plaque.
Quantification of ProSense in
ApoE -/- mice.
Multi-modality FMT – CT imaging
of lung carcinoma in adult mouse.
Quantification of AngioSense (green)
for tumor vascularity and ProSense
(red) for cathepsin activity.
Combined MRI and FMT in
mouse brain in a study of glioma
response to chemotherapy.
Image courtesy of Nahrendorf et al, ATVB, Jul 16, 2009.
Sequence courtesy of Weissleder, R., Nature 2008;452:580-589
Sequence courtesy of J. Chen, NeuroImage, 45 (2009) 360–369.
VISEN MEDICAL // MULTI-MODALITY IMAGING WITH FMT
Lung Metastasis
Bone Metastasis
Quantification in Spontaneous
0.00
11.41
22.82
34.23
Quantification of spontaneous
ovarian tumor model using
ProSense. The range of colors
represent the heterogeneity of the
tumor-specific signal.
PS750 ApoE Group 2:1-1
nM
45.65
0.00
Quantification of IntegriSense 750
as a biomarker for integrin activity
in bone metastasis, lung metastasis
and inflammation in the upper
lymph nodes.
50.00
100.00
150.00
nM
200.00
FMT tomography using ProSense to
quantify atherosclerotic plaque in 30
week ApoE-/- mice.
VISEN MEDICAL // RANGE OF APPLICATIONS
9
Application Example:
FMT Quantitative Imaging of Respiratory Disease
Quantifying Deep Tissue Biomarkers In Vivo
Multiplexing for Simultaneous
Biomarker Measurements In Vivo
With FMT, multiple agents can be imaged and quantified simultaneously for multiplexing analysis to evaluate a
number of biomarkers or pathways relating to a biological question. With the FMT 2500 LX, up to four different agents
can be imaged in the four separate channels, allowing for a 4-dimensional analysis of a particular application.
The ability to perform deep tissue imaging is essential for understanding the full extent of a disease pathway, for
evaluating the true nature of disease progression such as metastasis for confirming target biomarker expression, and
for truly measuring therapeutic effect. Such insights are not possible with planar fluorescent systems and are easily
achievable with FMT. The following examples show some of the possibilities within respiratory disease.
500.00
500.00
500.00
500.00
375.00
375.00
375.00
375.00
250.00
250.00
250.00
250.00
125.00
125.00
125.00
125.00
0.00
0.00
0.00
0.00
635 nm
670 nm
745 nm
785 nm
dye: 1-4
dye: 1-3
dye: 1-2
dye: 1-1
With the FMT 2500 LX, four agents can be imaged
simultaneously to allow for the quantification of four separate
biomarkers relating to a particular application.This image
(left) illustrates this capability with agents imaged in the
635 nm, 670 nm, 745 nm and 785 nm channels.
Image courtesy of Waterman, P and Nahrendorf, M, MGH/Harvard.
2D planar reflectance not
capturing deep tissue
information (left). FMT 3D
tomography quantifying
deep-seeded fluorescence in
the lung (right) to the picomole.
Avastin
Vehicle
80
IntegriSense
70
60
50
ProSense
Tumor Fluorescence (pmoles)
0.17
0.35
Counts/Energy
0.45
2D Planar
0
500
1000
5,000,000
4,000,000
80
550
750
nM
1000
ProSenseFluorescence (pmol)
325
Total Fluorescence (pmol)
100
Control
3,500,000
p < 0.1
60
40
p < 0.02 p < 0.009
20
0
0
0.03
0.3
3
Control
Dexamethasone Dose (mg/mouse)
100
rfu
3900
In Vivo FMT Tomography
AngioSense
Total Cells
4,500,000
100
Asthma+
Dex 3mg
3,000,000
Eocinophils
+
Macrophages
+
T cells
2,500,000
+/- statins
2,000,000
+
1,500,000
ProSense
MMPSense
+
+
+
+
+
+
Vehicle Avastin
Vehicle Avastin
IntegriSense
ProSense
Integri- OsteoSense Sense
+
+
+
+
+
Cat K
Measureable Biomarker, Pathway or Process
+
Plaque burden and profile
+
Measurement of vulnerable plaques
+
Identification of calcified plaques
+
Measurement of therapeutic response
Detection of aortic aneurysm
500,000
0
0
0.03
0.3
3
Control
Dexamethasone Dose (mg/mouse)
Multiplexing for Oncology
BAL Cell Counts
VisEn Fluorescent Agents
Agent
AngioSense
ProSense
MMPSense
+
+/- anti-angiogenic
+
+
Integri- OsteoSense Sense
Cat K
Measureable Biomarker, Pathway or Process
+
Changes in neovasculature
+
Viable tumor assessment versus effect of anti-angiognesis
treatment
+
+
+
+
+
+
+
+
+
+
+
+
+
VISEN MEDICAL // RESPIRATORY APPLICATION EXAMPLE
0
1,000,000
FMT quantification of ProSense in vivo of lungs following Dex dose response. FMT results align well with
postmortem lung fluorescence reflectance assessment (above) and to BAL cell counts (far right).
10
10
VisEn Fluorescent Agents
120
Asthma+
Dex 0.3mg
20
Multiplexing for Cardiovascular Applications
Agent
Asthma+
Dex 0.03mg
30
In this sequence, IntegriSense and ProSense are
imaged simultaneously to evaluate the effect of Avastin
on a tumor. Representative isosurface renderings of a
mouse treated with Avastin and a mouse treated with
vehicle are shown. Note the differential localization of
IntegriSense (blue), highlighting integrin presence, and
ProSense (red), quantifying cathepsin activity within the
same tumor. In addition, treatment with Avastin showed
quantitative changes in integrin imaging with as little as
1 week of treatment.
The following charts provide a review of the select cardiovascular and oncology biomarkers that can be evaluated
simultaneously using 2 (duplex), 3 (triplex) or 4 (quadplex) VisEn agents simultaneously:
3D FMT Tomography
Longitudinal Quantification of Disease Progression
and Therapeutic Efficacy In Vivo
Asthma
40
Multiplexed Imaging of
IntegiSense and ProSense
FMT Quantitative
Tomography Imaging
nM
1500
Tomographic
Quantification
Viable tumor assessment with estimate of immunologic
contribution to mass
+
Early response to anti-angiogenic treatment
+
Identification of bone and/or soft tissue metastasis sites
Measurement of therapeutic response
VISEN MEDICAL // MULTIPLEXED RESULTS
11
The Flexibility of FMT Quantitative Imaging:
Select either the FMT 1500 or the FMT 2500 LX
for your unique quantitative in vivo imaging needs.
™
™
™
More Channels.
More Multiplexing.
More Applications.
Whatever your needs, VisEn has a quantitative FMT platform to provide deeper insights to your biological
questions. Select the FMT 1500 for quantitative imaging in individual laboratories, in smaller facilities or for single
applications. The 4-channel FMT 2500 LX is available for laboratories requiring a broader range of applications and
extensive multi-modality capabilities.
The FMT Platform is now available
to quantify in vivo fluorescence in two
offerings — the FMT 1500 Model (two wavelengths
™
FMT 1500
FMT 2500 LX
Feature
Quantitative Tomography In Vivo Imaging System
Quantitative Tomography In Vivo Imaging System
Number of Quantitative FMT Channels
A two laser system operating at
A four laser system operating at 635 nm, 670 nm,
670 nm and 745 nm (excitation)
745 nm, and 785 nm (excitation)
Included
Included
™
Quantitative Tomography using
™
FMT for true quantification of deep
Wavelength
FMT Model
Easily Upgradable. Should a lab with a
FMT™ Channel Excitation Emmision Range
635 (New)
635 nm
650 – 670 nm
2500 LX
680
670 nm
690 – 740 nm
1500 / 2500 LX
750
745 nm
770 – 800 nm
1500 / 2500 LX
790 (New)
785 nm
805+
2500 LX
fluorescence to the picomole
EPI Fluorescence for Rapid Screening
Included (2-Channel)
Included (4-Channel)
of Superficial fluorescence
Simultaneous Multiplexing of
Included
at 670 nm and 745 nm) or the FMT 2500 LX model
(operating at four wavelengths – 635 nm, 670 nm,
745 nm and 785 nm). Four FMT channels allow
researchers to span a broader spectral fluorescence
range (from 650 – 850 nm) allowing greater imaging and
fluorescence quantification capability in vivo. In addition,
researchers will now be able to multiplex existing and
new agents and dyes providing even greater flexibility and
quantitative utility to the FMT 2500 LX.
FMT 1500 model want to expand its capability to four
wavelengths, the system is easily upgradable. There are
also a variety of additional expansion modules available.
This is all part of VisEn’s approach to providing open
access and flexibility to the unique and innovative needs
of the modern academic or pharmaceutical laboratory.
Included. Triplexing and quadplexing of 3 and
4 agents simultaneously also available with
Two Imaging Agents
the 4-channel FMT 2500 LX.
Multi-Modality Enabled
Includes DICOM image export.
Includes one (1) of the 4 available Multi-Modality Imaging
Adaptors and extended FMT DICOM Export Tools
Integrate Isoflurane-Based Anesthesia
RC2+ Integrated Isoflurane-based anesthesia
RC2+ Integrated Isoflurane-based anesthesia
not included.
included. Designed and fully optimized for use with
Open Architecture For Easy Data Access
The FMT is based on open data standards that enables everyone from the research scientist to global pharmaceutical
company to easily configure, network, access, share and integrate FMT quantification data to suit their workflow.
the FMT platform.
Next-Generation “Fast Recon”
_
Next-generation optimized algorithm enabling
lightning-fast image reconstruction
Agent Activation Package
Includes $5,000 of VisEn agents
Includes $10,000 of VisEn Agents
Number of TrueQuant Software Seats
1 (Host PC) + 1 additional Remote Software Seat
1 (Host PC) + 4 additional Remote Software Seats
Customer Activation
2 Days (On site)
2 Days (On site) + 3 additional days of
™
custom training available over 12 months
Training Session
(excluding travel)
Imaging Reporting Tools
_
Extensive tool kit for exporting experimental
set-up including study protocols, images and
associated quantification data
TrueQuant 3D software including
Included
Movie-Making functionality
12
VISEN MEDICAL // FMT 1500 AND FMT 2500 LX PRODUCT FEATURES
Included
Standard Data Formats:
Data from the FMT 2500
can be easily exported
as DICOM files for multimodality image fusion
and analysis.
Networked Instrumentation:
Multiple FMT instruments can be
networked across multiple sites with
image data stored centrally.
Open Architecture:
Data from both FMT 2500s and FMT
1500s can be equally stored and accessed
across a laboratory’s network.
Remote Analysis:
For high-throughput,
multi-user environments,
researchers can analyze
their data on the FMT PCs
or remotely with FMT
remote licenses.
VISEN MEDICAL // OPEN FMT ARCHITECTURE
13
VisEn’s Suite of Fluorescent
Imaging Agents and Dyes:
Enabling more insightful in vivo
and in vitro imaging results.
Unparalleled Range of Fluorescent Agents
for Imaging Multiple Disease Pathways and Biomarkers
Activatable Fluorescence Agents
Activatable agents are optically silent upon injection but are activated by interaction with specific protease
biomarkers of disease. Benefits include biologically-specific read-outs and high signal-to-noise at the target biology.
VisEn’s portfolio of fluorescent imaging agents utilize optimized
in vivo and in vitro chemistries and diverse mechanisms of action
to deliver breakthrough imaging data on biological targets,
pathways, biomarkers and processes in animal models.
Agent
Function
FAST Platform
The FAST platform represents the next generation of agents from VisEn. Utilizing
a novel small molecule design, the FAST agents offer improved specificity,
phamacokinetic profile and earlier imaging timepoints.
MMPSense 680
and 750 FAST
Imaging of MMP (Metalloproteinase) activity as involved in many
disease-related phenomena including cancer propagation, invasion and
metastasis, rheumatoid arthritis, and areas of cardiovascular disease.
ProSense 680 and 750
Imaging of changes in Cathepsin–based protease activity as seen in a number
of pathological states and disease-related events including rheumatoid arthritis,
cancer, atherosclerosis, angiogenesis and cardiovascular disease.
Cat K 680 FAST
Imaging of Cathepsin K activity in oncology applications involving
metastasis to the bone as well as a broad range of bone applications including
bone loss, tumor-induced osteolysis, and bone changes following arthritis.
ProSense Control
680 and 750
ProSense Control
VisEn’s agents allow:
•
•
•
Monitoring of disease progression and therapeutic response in vivo
Use of multiple agents simultaneously for multiplexed analysis of multiple pathways
True quantification to the picomole when imaged on the VisEn FMT, but able to be imaged
on all fluorescent imaging and IVM systems
VisEn’s fluorescent imaging agents also have the following attributes:
•
•
•
•
Synthetic, biocompatible chemistries for imaging specific target biologies
Injected intravenously (not engineered cells)
Activated, targeted and vascular
Biologically targeted agents (not dyes) for specificity of read-outs
Targeted Fluorescence Agents
Specially designed agents that actively target and bind to specific biomarkers. Benefits include the agents’ highly
specific targeting to key biologies.
Near Infrared Agents for Translatable In Vivo and In Vitro Results
Agent
Target
Validate your results using VisEn’s agents in your in vitro imaging and then correlate those biomarkers
in vivo using the FMT platform. As VisEn’s agents operate primarily in the near infrared range — also known
as the medical range, the results derived are translatable from preclinical research to clinical insights.
OsteoSense
680 and 750
Hydroxyapatite
IntegriSense
680 and 750
Targets αvβ3 expressed in oncology, atherosclerosis and
angiogenesis disease models.
Annexin-Vivo 750
In vivo targeting of membrane bound phosphatidyl exposed
during the early stages of apoptosis.
Insightful Results In Vivo with Multiple Animal Models
VisEn’s agents are tested and optimized for use with murine models but are also used widely in other animal
research models including rats and rabbits.
Vascular Fluorescence Agents
Vascular agents are a range of highly fluorescent in vivo imaging macromolecules that remain localized in
the vasculature for various periods of time to enable imaging of disease vasculature, vascular permeability
and angiogenesis.
14
VISEN MEDICAL // INTRODUCTION TO VISEN’S FLUORESCENT IMAGING AGENTS
Agent
Function
AngioSPARK
680 and 750
Imaging of vascularity, perfusion, and vascular permeability;
long pharmacokinetic profile.
Superhance 680
Imaging of vascularity, perfusion, and vascular permeability;
Short pharmacokinetic profile.
AngioSense
680 and 750
Imaging of vascularity, perfusion, and vascular permeability.
VISEN MEDICAL // LISTING OF VISEN FLUORESCENT AGENTS
15
NIR In Vivo Labels and Nanoparticles
AminoSPARK nanoparticles and VivoTag fluorochromes enable development of novel superbright NIR
fluorescent imaging agents with properties that are ideal for extended use in in vivo or in vitro imaging.
Agent
Function
VivoTag 680
Small molecule fluorochrome to label a target ligand. Optimized for
high-density loading.
VivoTag-S 680
and 750
Small molecule fluorochrome to label a target ligand. Optimized for
single molecule loading.
AminoSPARK 680
and 750
Nanoparticle fluorescent label for a target ligand. Superbright with extended
pharmacokinetic profile and the ability for multi-valent ligand coupling.
State-Of-The-Art Facilities
to Develop Leading Quantitative Imaging
Systems and Fluorescent Agents
1 day post MI
+ Spleen
Quantifying Multiple Biomarkers and Pathways Simultaneously Using
Application-Specific VisEn Fluorescent Imaging Agents
With a multitude of target-specific fluorescent agents and dyes, researchers can quantify multiple disease
pathways and biomarkers for the same biological question. In addition, using multiplexing, multiple agents can be
imaged simultaneously to generate multi-variable results and insights into disease biologies in vivo. The following
examples show some of the possibilities with oncology applications.
FMT Imaging of AngioSense, IntegriSense and ProSense
in a Model of Tumor Metastasis
Quantifying
Cathepsin
Activity
Control
4T1 – Injected
300
Lung Fluorescence (pmol)
Quantifying
Vascular
Activity
VisEn is dedicated to developing the industry’s
top quantitative imaging systems and
fluorescent imaging agents. With this leading
objective, we have built a state-of-the-art
facility and developed robust technology and
development processes that include extensive
325
550
nM
775 1000
chemistry, biochemistry, receptor-binding, and
microscopy-based labs, animal vivariums, and
in vitro-in vivo testing labs to enable robust
development and product performance. VisEn’s
R&D teams also work with new and existing
customers in our FMT in vivo demonstration
and teaching suite. Our Applied Biology and
Field Application Scientist teams assist in
experimental design, data analysis and in
helping our customers optimize their studies in
their labs and access key research areas.
The Highest In Vivo Imaging Agent QC and
Manufacturing Processes
for Reliable, Reproducible Results
High Cell Transfer
350
ProSense
100
– Spleen
250
200
150
100
50
0
0
10
14
Low Cell Transfer
70
60
Lung Fluorescence (pmol)
AngioSense
Quantifying
Integrin
Biomarkers
Cathepsin
50
Vascular
40
Integrin
30
20
10
IntegriSense
Simultaneous imaging of 3
different disease biologies
can be performed in vivo
and in real time using the
FMT to quantify AngioSense,
IntegriSense and ProSense.
Annexin-Vivo
Annexin-Vivo agent quantified
as a biomarker for apoptosis
in two mice, one (left) having
received Cyclophosphomide
treatment that induces
apoptosis in tumors and the
second (right) without the
treatment.
0
0
14
18
Quantifying
Apoptotic
Activity
[nM] Cyclophosphamlde: 1-1
-25
68.75
112.50
156.25
200.00
[nM] Controls: 2-1
-25
68.75
112.50
156.25
200.00
Quantifying
MMP
Activity
50
40
16
-25
68.75
112.50
156.25
200.00
-25
68.75
VISEN MEDICAL // VISEN FLUORESCENT LABELS AND NANOPARTICLES
112.50
156.25
200.00
Lung Fluorescence (pmol)
MMPSense
30
20
10
p=0.0042
0
Vehicle
FMT quantification of tumor
fluorescence (pmoles)
using FMT showing MMP
expression in a tumor-bearing
mouse (left) and a significant
decrease in MMPSense 750
FAST signal by NAC+panMMPi (88%, right).
VisEn’s agents are manufactured and tested
in our state-of-the-art facility and under strict
quality standards. This process is followed
throughout each of the new agent development
stages — from synthesis of prototypes and
test agents, In vitro testing, receptor binding,
selectivity profiling, through to in vivo testing,
ex vivo validation, fluorescence microscopy
and stability testing — to ensure our
finished agents perform to the highest
specifications and provide the most
reliable, reproducible results.
NAC/Pan-MMPi
VISEN MEDICAL // EQUIPPED AND STAFFED TO ENSURE QUALITY RESULTS
17
FMT 1500 and FMT 2500 LX:
System Specifications
™
™
FMT System In Vivo Imaging Parameters
•
Two Imaging modes: Reflectance Imaging and Quantitative Tomography
Currently available laser wavelengths:
•
•
•
•
•
The FMT 1500 includes TrueQuant 3D
software, two Imaging Cassettes, and
an 8-processor CPU for performing
quantitative tomography.
•
FMT 1500:
670 nm Channel (Excitation), Emission range = 690 – 740 nm
745 nm Channel (Excitation), Emission range = 770 – 800 nm
FMT 2500 LX:
635 nm Channel (Excitation), Emission range = 650 – 670 nm
670 nm Channel (Excitation), Emission range = 690 – 740 nm
745 nm Channel (Excitation), Emission range = 770 – 800 nm
790 nm Channel (Excitation), Emission range = 805+ nm
Animal Handling
•
•
•
Portable animal imaging cassette; multi-modality compatible
Integrated isoflurane-based gas anesthesia capability
Heated internal animal imaging chamber
System Dimensions
•
•
W × D × H: 46 cm (18") × 48 cm (19") × 89 cm (35")
Weight: 89 kg (195 lbs)
FMT 1500 & 2500 LX Imaging Systems
•
Delivered with computer, screen and pre-installed software.
TrueQuant Software
•
•
The FMT 2500 LX includes TrueQuant 3D
software, two Imaging Cassettes, RC2+
Integrated Anesthesia, a Multi-Modality
Adaptor, Fast Reconstruction software,
and an 8-processor CPU for performing
quantitative tomography.
One integrated application provides system control, data acquisition,
tomographic reconstruction, multiplexing capability, quantitative image
analysis, data export, and movie creation.
FMT 2500 LX includes advance Reporting Options, extended Multi-Modality
DICOM functionality and Fast Reconstruction software.
Optional Accessories
•
•
•
•
Additional Animal Imaging Cassettes
Multi-Modality Adapters (one included with the FMT 2500 LX); models
available for use with CT, MR, PET, and SPECT multi-modality imaging
and data co-registration
RC2+ Integrated Isoflurane-Based Anesthesia System (included with
the FMT 2500 LX)
Additional TrueQuant Software Site Licenses
™
VisEn biocompatible fluorescence agents and labels
18
The FMT 1500 and 2500 LX systems are optimized for use in combination
with VisEn fluorescence imaging agents and labels for in vivo fluorescence
imaging. Both FMT systems are fully compatible with the complete range of
VisEn fluorescence imaging agents and labels. Choose from ready-to-use
activatable, targeted or vascular agents or design your own imaging agents
with VisEn’s VivoTag and NanoSpark optimized in vivo labels.
™
™
Real-time 3D tomographic quantification to the picomole3 of
metastases, angiogenesis, apoptosis, therapeutic efficacy, an
disease progression. VisEn has pioneered fluorescence-base
Quantitative Tomography for in vivo imaging research. Imagin
systems based on VisEn’s proprietary FMT technology provid
non-invasive, whole body, deep tissue imaging in small anim
models and generate 3D, information-rich results. These sys
are used for research in oncology as well as inflammatory,
pulmonary, cardiovascular and skeletal disease. Biological ta
and pathways can be monitored and quantified in real time –
adeeper understanding of the biology underlying disease me
and therapeutic response. Real-time 3D tomographic quantifi
to the picomole of metastases, angiogenesis, apoptosis, ther
efficacy, and disease progression. VisEn has pioneered fluore
based Quantitative Tomography for in vivo imaging research.
systems based on VisEn’s proprietary FMT technology provid
invasive, whole body, deep tissue imaging in small animal m
and generate 3D, information-rich results. These systems are
used for research in oncology as well as inflammatory, pulmo
cardiovascular and skeletal disease. Biological targets and p
can be monitored and quantified in real time – giving a deep
understanding of the biology underlying disease mechanisms
therapeutic response. Real-time 3D tomographic quantificati
the picomole of metastases, angiogenesis, apoptosis, therap
efficacy, and disease progression. VisEn has pioneered
fluorescence-based Quantitative Tomography. These systems
used for research in oncology as well as inflammatory, pulmo
cardiovascular and skeletal disease. Biological targets and p
VISEN MEDICAL // OVERVIEW OF SERVICES
19
True quantification to the picomole
VisEn’s FMT In Vivo Imaging System and
Fluorescent Imaging Agent Solutions
VisEn Medical Inc.
45 Wiggins Avenue
Bedford, MA 01730
T. 781.430.5400
F. 781.938.7136
E. [email protected]
© 2009. The VisEn logo, MMPSense™, IntergriSense™,
FMT 2500™ LX, FMT 1500™, TrueQuant™ and FMT™ are
trademarks of VisEn Medical Inc. AngioSense®, VisEn®,
OsteoSense®, AngioSpark®, NanoSpark®, VivoTag® and
ProSense® are registered trademarks of VisEn Medical Inc. All
third party trademarks are the property of their respective owners.
VisEn’s fluorescent agents and labels and FMT system are
covered under several issued and pending US and international
patents. VisEn products are not available for resale or other
commercial use without a specific agreement.
www.visenmedical.com
20
VISEN MEDICAL // OVERVIEW OF APPLICATIONS
VisEn Medical products may be used for a wide range of different
imaging applications. Some applications may require a license
from a third party. Users are advised to consult with counsel
to determine whether such a license from a third party may be
required in order to perform a particular imaging application.
VisEn Medical disclaims any and all responsibility for, or liability
with respect to, any patents or other intellectual property rights
of third parties.