Siemens Healthcare Molecular Imaging Introducing Explora One Xavier Battle, Ph.D. General Manager Siemens Cyclotron & Chemistry Solutions Copyright © Siemens AG 2011. All rights reserved.
Siemens Healthcare Molecular Imaging
Introducing
Explora One
Xavier Battle, Ph.D.
General Manager
Siemens Cyclotron &
Chemistry Solutions
Copyright © Siemens AG 2011. All rights reserved.
Siemens Healthcare Molecular Imaging
PET Imaging
One of the fastest growing tests
30% procedure growth
(Source IMV report of average US PET growth per year in the recent 7 years; 0.248 millions in 2001 to 1.521 millions in 2008 )
Siemens Healthcare Molecular Imaging
PET.CT Scanner
Time Magazine Invention of the Year 2000
Siemens Healthcare Molecular Imaging
FDG PET
The very first winning combination
Siemens Healthcare Molecular Imaging
Oncology syngo®.via Symbia.net
Cardiology Clinical Solutions
Biomarkers
Inveon™
Customer Care
Symbia S Symbia E Symbia T c.cam mMR
Biograph™ Symbia™
Eclipse™
Preclinical
PETNET Explora™
Preclinical Imaging Solutions PET
SPECT CT Multimodality Inveon Research Workplace
General NM
TruePoint mCT mCT 20 Excel
Siemens Molecular Imaging
Product overview
Neurology
Siemens Healthcare Molecular Imaging
Explora One
One Integration. Infinite Possibilities.
Introducing Explora One
The Choice for PETNET Solutions
A wide offering through partnership
Siemens Healthcare Molecular Imaging
Introducing
Explora One
Martin Cordell, Ph.D.
Product Manager
Siemens Cyclotron &
Chemistry Solutions
Copyright © Siemens AG 2011. All rights reserved.
Siemens Healthcare Molecular Imaging
Explora One
One Integration. Infinite Possibilities.
system for 18F PET
imaging
biomarker
production
One
Siemens Healthcare Molecular Imaging
Explora One
One Integration. Infinite Possibilities.
One Easy,
Integrated
Workflow
One System,
Infinite
Possibilities
Siemens Healthcare Molecular Imaging
Explora One
One Integration. Infinite Possibilities.
One Easy,
Integrated
Workflow
One System,
Infinite
Possibilities
Siemens Healthcare Molecular Imaging
Web UI Aids
cGMP
Efficient Connectivity
Browser-based user interface for remote operation, monitoring and troubleshooting
Rapid diagnostics to maximize uptime with Siemens Remote Service
Simplified Quality Compliance
Simplified audit tracking with tiered individual user accounts with password protection
Disposable cassettes reduces user error and minimizes cleaning validation process
Easy Workflow
Reduced interaction for easy setup, minimizing user errors
Integrated user interface provides increased production reliability
Intuitive UI, simpler to learn
Equipment Integration
Integrated synthesis, purification and reformulation
One mini-cell
Lower total equipment cost
Lower maintenance costs
Equipment
Integration
Simplified Quality
Compliance
Efficient
Connectivity
Easy
Workflow
Explora One
One Easy, Integrated Workflow
Siemens Healthcare Molecular Imaging
One Easy, Integrated Workflow
Equipment integration
Additional cassette
manifold for further
processing, e.g.,
reformulation
HPLC drawer for
HPLC purification
Primary cassette
manifold for synthesis
and cartridge
purification
Siemens Healthcare Molecular Imaging
Explora One
One Integration. Infinite Possibilities.
One Easy,
Integrated
Workflow
One System,
Infinite
Possibilities
Siemens Healthcare Molecular Imaging
Wider Variety Switch easily
Day 3
Day 2
Day 1
Create new sequences
` Flexible Production Sequences
Allows end users to create new production sequences to expand offerings and share with colleagues
Utilize and/or improve production sequences shared by colleagues
Imaging Biomarker Variety
Wide range of imaging biomarker production sequences to meet demand for variety of PET applications
Multiple consumable suppliers drives competitive pricing
Currently >8 imaging biomarkers are available
Flexible Imaging Biomarker Production
Comprehensive integrated production system supports complex imaging biomarker synthesis processes
Cassette-based disposable fluid pathway allows users to switch easily between imaging biomarkers
Flexible
Production
Sequence
Imaging
Biomarker
Variety
Flexible Imaging
Biomarker
Production
Divisional Sales Meeting Imaging & IT 2009
Explora One
One System, Infinite Possibilities
Siemens Healthcare Molecular Imaging
Explora One
One Integration. Infinite Possibilities.
One Easy,
Integrated
Workflow
One System,
Infinite
Possibilities
Siemens Healthcare Molecular Imaging
Explora One One Integration. Infinite Possibilities.
Copyright © Siemens AG 2013. All rights reserved.
Siemens Healthcare Molecular Imaging
Siemens Explora One:
The Choice for PETNET
Solutions James Cook
Vice President,
PETNET Global Sales
Copyright © Siemens AG 2011. All rights reserved.
Siemens Healthcare Molecular Imaging
Divisional Sales Meeting Imaging & IT 2009 The choice for PETNET Solutions
Siemens Healthcare Molecular Imaging
Future
Perspective Amyloid*
Ramp-up
Business
Environment
* Amyloid imaging biomarker production
Siemens Healthcare Molecular Imaging
Divisional Sales Meeting Imaging & IT 2009 The choice for PETNET Solutions
Siemens Healthcare Molecular Imaging
Future
Perspective Amyloid*
Ramp-up
Business
Environment
* Amyloid imaging biomarker production
Siemens Healthcare Molecular Imaging
PETNET Solutions
Delivering molecular imaging biomarkers
The SafetyNetTM guarantees reliable delivery of molecular biomarkers to hospitals, clinics and research facilities
Albany Cleveland Houston Los Angeles Phoenix Spokane International Locations
Albuquerque Columbia Indianapolis Louisville Pittsburgh St. Louis Korea
Atlanta Dallas Irvine Minneapolis Portland Tampa United Kingdom
Baltimore Denver I Jacksonville Nashville Raleigh Durham Tulsa Australia
Birmingham Denver II Kansas City New Orleans Sacramento Winston Salem Spain
Boston Detroit Knoxville Omaha San Antonio France
Chicago Ft Lauderdale Las Vegas Palo Alto San Diego India
Cincinnati Hackensack Little Rock Philadelphia Seattle
Siemens Healthcare Molecular Imaging
PETNET Solutions
Delivering molecular imaging biomarkers
Complete radiopharmaceutical
value chain encompassing
discovery, clinical trials and
manufacturing and distribution
Largest global cyclotron-
equipped radiopharmaceutical
manufacturing and distribution
network
Standardized equipment and
processes provides consistent
production of
radiopharmaceuticals at
all sites throughout the world
Siemens Healthcare Molecular Imaging
Divisional Sales Meeting Imaging & IT 2009
PETNET Solutions
Clinical non-proprietary imaging biomarkers
Sodium fluoride F 18
(18F NaF)
Ammonia N 13
(13N NH3)
Fludeoxyglucose F 18
(18F FDG)
Courtesy University Hospital, Tuebingen, Germany
Siemens Healthcare Molecular Imaging
Divisional Sales Meeting Imaging & IT 2009
PETNET Solutions
Clinical proprietary imaging biomarkers
Siemens Healthcare Molecular Imaging
Divisional Sales Meeting Imaging & IT 2009
The choice for PETNET solutions
Siemens Healthcare Molecular Imaging
Future
Perspective Amyloid*
Ramp-up
Business
Environment
* Amyloid imaging biomarker production
Siemens Healthcare Molecular Imaging
PETNET Solutions
Network of manufacturing facilities for Amyloid*
PETNET Solutions
Other distributors
PETNET Solutions and other suppliers
United States Active Production Sites
Atlanta Boston Chicago Dallas Denver Hackensack Houston Jacksonville Los Angeles
Minneapolis Palo Alto Philadelphia Raleigh Saint Louis Seattle Fort Lauderdale Cleveland
New Orleans Pittsburgh San Diego Sacramento
Pending Production Sites Charlottesville Detroit Indianapolis Nashville
Copyright © Siemens AG 2013. All rights reserved. * Amyloid imaging biomarker production – w orkflow produced on Explora GNLC. Based on 2.5 hours normal drive time. Actual time may vary.
Siemens Healthcare Molecular Imaging
PETNET Solutions
Amyloid* ramp-up
Deliver Reliability*
YTD – April 2013
% R
elia
bilit
y
96%
100
95
90
85
80
>1,900
Doses shipped as
of April 2013*
* Data on f ile. Amyloid imaging biomarker production – workflow produced on Explora GNLC.
Siemens Healthcare Molecular Imaging
Preparation
Explora One
The choice for PETNET Solutions
Conventional Complex Workflow for Amyloid*
Critical Steps
Cleaning Bombard Target
Sterile Filtering
Synthesis Purification Final Product
1 2 3 4 5 6 7 8 9 10 11
* Amyloid imaging biomarker production
Reformulation Dispensing Quality Control
Quality Control
Preparation
Simplified
Bombard Target
Sterile Filtering
Integrated synthesis, purification and reformulation
Final Product
1 2 3 4 5 6 7 8
Dispensing Quality Control
Quality Control
Explora One Easy Workflow for Amyloid*
Siemens Healthcare Molecular Imaging
Separate purification and reformulation modules
Two mini-cells
Higher total equipment cost
Higher maintenance costs
Integrated synthesis, purification and reformulation
One mini-cell
Lower total equipment cost
Lower maintenance costs
Explora One
The choice for PETNET Solutions
Conventional Complex Workflow Explora One Easy Workflow
Critical Steps
Synthesis Purification Reformulation
1 2 3
Simplified
1
Integrated synthesis, purification and reformulation
Siemens Healthcare Molecular Imaging
Increased user interaction and more user errors
Multiple user interfaces decreases production reliability
Complex to learn
Reduced interaction for easy setup, minimizing user errors
Integrated user interface provides increased production reliability
Intuitive UI, simpler to learn
Explora One
The choice for PETNET Solutions
Conventional Complex Workflow Explora One Easy Workflow
Critical Steps
1 2 3
Simplified
1
Synthesis Purification Reformulation Integrated synthesis, purification and reformulation
Siemens Healthcare Molecular Imaging
Amyloid* Ramp-up
Conventional complex workflow – high risk
N2
Mini-Cell 1 Mini-Cell 2 Hot Cell Cri
tic
al S
tep
s
1. Start synthesis process on synthesis module
2. Use synthesis module to push product onto pre-HPLC purification cartridge
3. Switch fluid path from waste to collection vials
4. Pull 4 ml of air to fill HPLC loading loop
5. Collect HPLC fraction containing product
6. Push diluent into HPLC fraction to dilute and mix
7. Switch on nitrogen to push product onto reformulation cartridge
8. Switch fluid path to syringe for wash and elution
9. Push wash fluid through reformulation cartridge
10. Move fluid path from waste to product vial using manipulators in hot cell
11. Push eluent through reformulation cartridge
12. Chase product into product vial by pushing more wash fluid
Synthesis
Software Purification Module
Software
Many manual steps
Many manual steps
7 8 9 10 6
5
4
3
2
1
11
12
* Amyloid imaging biomarker production
Siemens Healthcare Molecular Imaging
Amyloid* Ramp-up
Easy Explora One workflow – simplified
Mini-Cell
Hig
h R
isk
Integrated Control Software
Sim
pli
fie
d
1. Start synthesis process on synthesis module
2. Collect HPLC fraction containing product
2 1
* Amyloid imaging biomarker production
Siemens Healthcare Molecular Imaging
Divisional Sales Meeting Imaging & IT 2009
Explora One
The choice for PETNET solutions
Siemens Healthcare Molecular Imaging
Future
Perspective Amyloid*
Ramp-up
Business
Environment
* Amyloid imaging biomarker production
Siemens Healthcare Molecular Imaging
Explora One
PETNET solutions future perspective
Explora One
Allows PETNET solutions to use the same module to produce many different imaging biomarkers
Open source platform and cassette-based system allows for easy adoption of new synthesis sequences
Benefits
Reduces cost of additional modules and mini-cells
Facilitates expansion to new imaging biomarkers easily for production and distribution
Switch easily
Day 3
Day 2
Day 1
Siemens Healthcare Molecular Imaging
A wide offering through
partnership
Dr. Marco Mueller
Senior Scientist
ABX Advanced
Biochemical Compounds
Copyright © Siemens AG 2011. All rights reserved.
ABX advanced biochemical compounds
ABX products for Siemens Explora One
ABX advanced biochemical compounds
[18F]F-FDG Yield 70 % [18F]F-FET Yield 25 %
[18F]F-FMISO Yield 25 % [18F]F-CHOLINE Yield 25 %
[18F]F-NaF Yield 90 % [18F]F-FLT Yield 20 %
[18F]F-FES Yield 20 % [18F]F-SFB Yield 20 %
What is available?
[18F]F-ACETATE Yield 35 %
ABX advanced biochemical compounds
COOtBu
NHTrMOMO
NO2
H O
COOtBu
NHTrMOMO
18F
H O
[18F]-, K222
K2CO3
DMSO
110 °C
m-CPBA
MeCN
55 °C
2 3
COOtBu
NHTrMOMO
O
18F
COOH
NH2HO
OH
18F
4 6-[18F]-fluoro-L-DOPA (1) >98% ee
O
H
HCl
50 °C
What is new?
[18F]F-L-Dopa Yield 10 %
• n.c.a method (high specific activity)
• enantiomeric purity 99%
• starting activities up to 10 Ci
• “HPLC cleaning“
ABX advanced biochemical compounds
Complete solutions:
•Easy to use
•Produced According to ICH Guideline
Q7, Chapter 19
•Cassettes gamma-sterilized
•Precursor, Kit , Cassette,
Sequence
ABX advanced biochemical compounds
Kit description: valve 1) recovery of O-18water, no changes compared to FDG valve 2) QMA, no changes compared to FDG
valve 3) 7ml acetonitrile, no changes compared to FDG
valve 4) 30 ml syringe, no changes compared to FDG
valve 5) 25mg FLT-Precursor dissolved in 2ml of acetonitrile
valve 6) reactor inlet, no changes compared to FDG valve 7) 3ml syringe with 2,4 ml of 1N NaOH
valve 8) 100 ml waterbag, add 2ml of ethanol before placing
the waterbag valve 9) 20 ml syringe of (10/1) water/ethanol
valve 10) 3 ml syringe with 1,5 ml 2N HCl
valve 11) out to final with pre-conditioned Alumina-N light cartridge, sterile filter with needle and vented filter,
add 3ml of buffer solution to the final vial
valve 12) pre-conditioned cleaning cartridges (PS-H, WAX, HLB) valve 13) tubing for cleaning cartridges
valve 14) 30 ml syringe, no changes compared to FDG
valve 15) no changes compared to FDG
ABX advanced biochemical compounds
Sta
ge
nu
mb
er
Me
ssa
ge
ap
pe
ari
ng
on
th
e
scre
en
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e 1
, le
ft : p
ositio
n o
f th
e
pis
ton
(3
mm
=e
mp
ty)
Syri
ng
e 2
, m
idd
le : p
ositio
n o
f
the
pis
ton
(3
mm
=e
mp
ty)
Syri
ng
e 3
, ri
gh
t : p
ositio
n o
f th
e
pis
ton
(3
mm
=e
mp
ty)
Ne
ga
tive
pre
ssu
re (
va
cu
um
= -
1
atm
.=0
)
Co
nd
itio
n
Co
nd
itio
n 2
De
lay fo
r co
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itio
n
Ju
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to
sta
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Su
pe
rvis
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win
do
w
rot a
ct 1
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ial
rot a
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ft, r
eco
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rid
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rot a
ct 3
, a
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ton
itri
le
rot a
ct 4
, 3
0m
l syri
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ate
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rot a
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, F
LT
Pre
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ct 6
, r
ea
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r in
let
rot a
ct 7
, 2
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l syri
ng
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rot a
ct 8
, w
ate
rba
g / e
tha
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rot a
ct 9
, fin
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rot a
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e H
Cl
rot a
ct 1
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fica
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n A
lum
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-
rot a
ct 1
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rot a
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rot a
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4, 3
0m
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e,
rot a
ct 1
5, r
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va
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1-1
5, e
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6, a
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va
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7, r
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rvo
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FL
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-7, "R
ea
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re
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rot a
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rig
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X X X
V P 1/100 sec 1/10 °C mm mm mm 1/100 bar sec. 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 0 1 2 3 4 5 6 23 8 9 10 11 12 13 14
0 Hooking on the syringes 500 0 92 92 92 -50 0 0 1 0 1 1 1
1 Hooking on the syringes 100 0 92 40 20 -50 128 0 30 184 1 1 1 1 1
2 Hooking on the syringes 500 0 92 40 20 -50 0 0 23 0 1 1 1 1
3 Hooking on the syringes 500 0 92 40 20 -50 0 0 1 0 1 1 1 1 1
4 Hooking on the syringes 500 0 92 40 20 -50 0 0 1 0 1 1 1 1
5 Hooking on the syringes 500 0 92 40 20 -50 0 0 1 0 1 1 1 1 1
6 Hooking on the syringes 500 0 10 40 20 -50 128 0 30 184 1 1 1 1
7 Hooking on the syringes 100 0 0 40 10 -50 128 0 30 184 1 1 1 1
8 Hooking on the syringes 1000 0 0 40 35 -40 128 0 30 184 1 1 1 1
9 Pressurising final solution 100 0 0 40 20 -40 128 0 30 0 1 1 1 1 1
10 Pressurising waterbag 100 0 0 40 0 -40 128 0 30 184 1 1 1 1 1
11 Depressurising left syringe 2000 0 0 40 0 -80 0 0 1 0 1 1
12 Depressurising left syringe 2000 0 0 40 0 -80 0 0 1 0 1 1 1
13 Depressurising left syringe 2000 0 0 40 0 -80 0 0 1 0 1 1
14 Depressurising left syringe 2000 0 0 40 0 -80 0 0 1 0 1 1 1
15 Rinsing manifolds with acetonitrile 100 0 0 40 0 -35 64 0 120 184 1 1 1
16 Rinsing manifolds with acetonitrile 100 0 0 40 0 -35 0 0 1 0 1 1 1 1
17 Rinsing manifolds with acetonitrile 500 0 0 40 0 -65 0 0 1 0 1 1 1
18 Rinsing manifolds with acetonitrile 300 0 0 40 0 -65 0 0 1 0 1 1 1 1
19 Pressurising acetonitrile vial 500 0 0 40 0 -65 0 0 1 0 1 1 1 1
20 Pressurising acetonitrile vial 200 0 0 40 0 -65 0 0 1 0 1 1 1 1
21 Pressurising acetonitrile vial 500 0 0 40 0 -65 0 0 1 0 1 1 1 1
22 Pressurising acetonitrile vial 200 0 0 40 0 -65 0 0 1 0 1 1 1 1
23 Pressurising acetonitrile vial 500 0 0 40 0 -65 0 0 1 0 1 1 1 1
24 Pressurising acetonitrile vial 200 0 0 40 0 -65 0 0 1 0 1 1 1 1
25 Pressurising acetonitrile vial 500 0 0 40 0 -65 0 0 1 0 1 1
26 Pressurising acetonitrile vial 100 0 0 40 0 -65 0 0 1 0 1 1 1
27 Rinsing manifolds with acetonitrile 200 0 0 40 0 -65 0 0 1 0 1 1 1 1 1
28 Rinsing manifolds with acetonitrile 500 0 0 40 0 -65 0 0 1 0 1 1 1
29 Rinsing manifolds with acetonitrile 500 0 0 40 0 -65 0 0 1 0 1 1
30 Rinsing manifolds with acetonitrile 100 0 0 40 0 -65 0 0 1 0 1 1 1
31 Rinsing manifolds with acetonitrile 200 0 0 40 0 -65 0 0 1 0 1 1 1 1 1
32 Rinsing manifolds with acetonitrile 500 0 0 40 0 -65 0 0 1 0 1 1 1
33 Rinsing manifolds with acetonitrile 500 0 0 40 0 -65 0 0 1 0 1 1
34 Rinsing manifolds with acetonitrile 100 0 0 40 0 -65 0 0 1 0 1 1 1
35 Rinsing manifolds with acetonitrile 200 0 0 40 0 -65 0 0 1 0 1 1 1 1 1
36 Rinsing manifolds with acetonitrile 500 0 0 40 0 -65 0 0 1 0 1 1 1
37 Rinsing manifolds with acetonitrile 500 0 0 40 0 -65 0 0 1 0 1 1
38 Rinsing manifolds with acetonitrile 100 0 0 40 0 -65 0 0 1 0 1 1 1
39 Rinsing manifolds with acetonitrile 200 0 0 40 0 -65 0 0 1 0 1 1 1 1 1
40 Rinsing manifolds with acetonitrile 2000 0 0 40 0 -30 64 0 120 41 1 1 1 1 1
41 Rinsing manifolds with acetonitrile 1000 0 0 40 0 -30 0 0 1 0 1 1 1 1 1
42 Waiting for operator reply 100 0 0 40 0 -30 10 0 1 42 1 1
43 Recovering the target water 100 0 0 40 0 -20 64 0 180 44 1 1 1
44 Recovering the target water 6000 0 0 40 0 -20 0 0 1 0 1 1 1 1 1 1
45 Recovering the target water 6000 0 0 40 0 -30 0 0 1 0 1 1 1 1 1 1
46 Recovering the target water 3000 0 0 40 0 -50 0 0 1 0 1 1 1 1 1 1
47 Recovering the target water 1000 0 0 40 0 -30 0 0 1 0 1 1 1 1 1
48 Recovering the target water 100 0 0 40 0 -30 64 0 180 49 1 1 1 1
49 Transfer of the eluent 500 0 0 40 0 -30 0 0 1 0 1 1 1 1
50 Transfer of the eluent 500 0 0 40 0 -30 0 0 1 0 1 1 1 1
51 Transfer of the eluent 100 0 0 40 0 -10 64 0 180 52 1 1 1 1
52 Transfer of the eluent 500 0 0 40 0 -10 0 0 1 0 1 1 1 1
53 Transfer of the eluent 500 0 0 40 0 -10 0 0 1 0 1 1 1 1
54 Elution of fluoride 100 0 0 40 0 -5 64 0 180 55 1 1 1 1 1 1
55 Elution of fluoride 1000 0 0 40 0 -5 0 0 1 0 1 1 1
56 Elution of fluoride 500 0 0 40 0 -25 8192 0 120 53 1 1 1 1 1
Transfert->PLCTransfert->PLC
Customized Sequences :
ABX advanced biochemical compounds
Documents for QA, QC:
ABX advanced biochemical compounds
How can we help with QC?
Monographs (Pharmeuropa) for FDG, FLT, FMiso, NaF and “FET“
Literature and Posters...
ABX advanced biochemical compounds
ABX advanced biochemical compounds
ABX advanced biochemical compounds
Copyright © Siemens AG 2013. All rights reserved.
Thank You!