NEW DEVELOPMENTS

OF PET

Hussein M. Abdel-Dayem, M.D.

Chief, Nuclear Medicine
St. Vincent’s Medical Centers of New York

Professor of Radiology
New York Medical College
 MOTIVATIONS FOR
DEVELOPMENTS

IMPROVED
PATIENT
CARE
FINANCIAL COMPETITION
 US Cancer incidence and reimbursement
drive demand for 2.2M PET procedures
Total potential procedures based on clinical utility, and current reimbursements
Ca nce r Inc ide nce Es timate d proce dure s
Sc ree ning Diagnos is s taging Follow up Total
Breas t 193,700 - - 108,864 384,783 493,648
Lung 184,600 - 147,311 92,062 442,804 682,176
Colore cta l 135,400 - 68,400 61,127 288,644 418,171
Lymphoma 63,600 - 32,250 30,298 138,785 201,333
Melanoma 56,400 - 17,000 16,417 91,372 124,789
He ad & Neck 30,100 42,225 37,048 168,365 247,638
Es ophage al 13,200 9, 900 1, 584 4, 752 16,236
FDG Viability 45,000
Epileps y 15,000
TOTAL 2, 243,991

Based on 0.2% of the population (280M) having epilepsy; 25% cases being refractory and 12% where PET is applicable

FDG Viability Based on 6M NM cardiac procedures each year; 3% of which are Myocardial Viability cases and 25% where PET is needed

Current procedures = 160,000 annual 2001 ( ref: IMV 2001 Panel Survey)
Procedures performed on PET (83%) and Coincidence (17%) in 2001,
Coincidence proportion down to 10% in 2002 and 0% in 2003 ( ref: IMV 2001 Panel Survey)
 NEW DEVELOPMENTS

NEW
INSTRUMENTATION APPLICATIONS

RADIO-
PHARMACEUTICALS
OBJECTIVES OF NEW DEVELOPMENTS
IN INSTRUMENTATION:

• High Sensitivity - short acquisition time

• High resolution - better medical care
• Better mapping of functional and
morphological imaging
 IN 1997 NEW DEVELOPMENTS
WERE:

• Approved regulations for radiopharmaceutical

production
• Reimbursements for F-18 FDG PET Studies for
Pulmonary Nodules
• Multifunctional Gamma Cameras
EXPANDED REIUMBURSEMENTS
IN 2002:
• Lung, Malignant Lymphoma, Recurrent
Colorectal Cancer, Malignant Melanoma
Head & Neck Cancer, Esophageal Cancer,
Recurrent or Metastatic Breast Cancer and
Thyroid Cancer
• Epilepsy
• Myocardial viability and perfusion
IN 2003:
• Expected wide acceptance for coverage for
other malignant diseases and for Dementia
 IN 2003:
NEW RADIOPHARMACEUTICALS
OBJECTIVES:
• More specific
• Expanded applications
• Dosimetry for therapy
F-18 RADIOPHARMACEUTICALS:
• Advantages of F-18
• F-18 Methionine
• F-18 Choline
• F-18 Estradiol
• F-18 Fluorodopa
I-124 RADIOPHARMACEUTICALS:
• Monoclonal antibodies
• Thyroid cancer
IN 2003: NEW DEVELOPMENTS IN
PET INSTRUMENTATION
• New detectors
• Image fusion
• Imported images for software image fusion
• Combination of CT/PET
• Developments of new software to meet the
demands of the new technology for:
• CT attenuation correction
• Image fusion
• Radiotherapy planning
• Respiratory gating
• New masks for radiotherapy planning
 PET Scanner CTQ’s
PET/CT Scanner

rm n
n

o
i ty
vi ty

ut io

Un ol ut i

ast

Fra t ter
n
cti o
ti
PET Scanner Design

I
so l
nsi

ntr

RO
i fo

a
s

Sc
Re

Co
Re
Se
Considerations
Crystal Size
Crystal Material
Crystal Spacing
Ring Diameter
Collimation
Shielding
Light Collection System
Front-End Electronics
Data Pipeline
Pre-Processing
Reconstruction
Strong Influence Moderate Weak None
 PET SCINTILLATORS
• NaI (TI) (1940s, Hofstadter
Hofstadter))
(ECAT II-1977, ADAC CPET-1996)

• BGO (1970s, Weber)

(ECAT 911-1982, GE Advance-1994)

• GSO (1980s, Takagi)

(Scanditronix PC-2048, 1983)

• LSO (1990s, Melcher)

(ECAT ACCEL-2000)
 Detector Material Comparison
Detection efficiency of PET materials
(% ) 100
90 82
D etection E fficiency
80
80 74
70

Better
60 56
50
40
30
20
10
0
N aI BG O LSO G SO
Crystal thickness 25.4 mm 20 mm 20 mm 20 mm
Data simulation Karp, et. al.

ADAC - A PHILIPS Medical Systems Company

 Detector Material Comparison

Scintillation Speed of PET materials

300 300

250 230

better
Decay Time (nsec)

200

150

100
60
50 40

0
BGO NaI GSO LSO

Faster scintillators can decrease dead time.

ADAC - A PHILIPS Medical Systems Company

 Detector Material Comparison

Energy resolution of PET devices

25
Energy Resolution (%)

20

better
15

10

0
BGO-PET LSO-PET NaI-PET GSO-PET

Data shown based on manufacturers data sheets or published results of experimental devices
ADAC - A PHILIPS Medical Systems Company
 Comparison of materials
NaI BGO LSO GSO YSO

Fast/Slow 60/300 60/600

Decay Time (ns) 230 40 70
(Ratio) (1/10) (7/1)

Relative Light Output (PMT) 100 15 75 20 120

Relative Light Output (APD) 100 30 80 40 105
Peak Emission (nm) 410 480 420 430 430
Index of Refraction 1.85 2.15 1.82 1.85 1.80
Density (g/cm3) 3.67 7.13 7.35 6.71 4.54
Effective Z 50 73 65 58 28
1/µ at 511 keV (mm) 30.7 11.6 12.3 15.0 44.4
Table courtesy of R. Lecomte
Lecomte,, Universite de Sherbrooke

ADAC - A PHILIPS Medical Systems Company

 Good energy resolution reduces scatter in 3D
System scatter fraction as a function of the
lower level discriminator (LLD) threshold LLD

0.45

0.4

0.35

0.3
Scatter Fraction

0.25

0.2

0.15
Energy Threshold (keV)
0.1 • GSO 400
0.05 • NaI 435
0 • LSO 350
0 100 200 300 400 500 600
Energy Thre shold
• BGO 350

Data: ADAC-UGM
ADAC - A PHILIPS Medical Systems Company
 Good energy resolution reduces randoms in 3D
Randoms are related to the singles
System energy spectra for System randoms fraction as
singles and coincidences a function of the lower level
discriminator (LLD) threshold
6000

R andom s relative
14
5000
12

to 43 5 keV
4000
Counts

10
Singles Mode
3000 8
2000 6
4
1000
Coincidence Mode 2
0
0
0 200 400 600 800 1000 200 300 400 500 600
Energy (keV) Lo w er E ne rgy threshold (keV )

Data: ADAC-UGM Random fraction goes down as you

raise the LLD
ADAC - A PHILIPS Medical Systems Company
 Image Fusion:
WHY?
• Greater diagnostic confidence
– referring & interpreting MD, less intra-observer and
inter-observer variability
– previously relied on spatial sense to mentally overlap
images from several modalities
– Needed for all locations
• Improved patient management, treatment delivery
and evaluations
• Improved accuracy of anatomic localization
• Reduces time and cost of associated repeat exams
in resolving equivocal cases
 Image Fusion

• Guide surgery or biopsy

• Oncology
– fibrosis vs. active tumor
– evaluation of therapy response
– uptake of FDG vs. size on CT
• Radiotherapy Applications
– Tailor field size to viable tumor
– Assessment of residual mass on CT post therapy
– Radiotherapy masks
Image Fusion: CT & FDG Coincidence Imaging

Epitheliod Sarcoma after resection

ADAC - A PHILIPS Medical Systems Company

DIFFERENT APPROACHES FOR
CT/PET COMBINATION:
• Incomplete circle of detectors “Seimens”
allows both CT and PET on same gantry,
has problems of loss of sensitivity, heat output
• CT & PET separate connected design
“GE, CTI and Seimens”
• CT and PET on two separate gantries
unconnected “Phillips”
 Gemini

PET
CT

ADAC - A PHILIPS Medical Systems Company

 Optimized for
Interventional Radiology
Identify FDG positive lymph node using PET.
Biopsy using CT.
Integrated Operation Separated Operation
(CT/PET Imaging) (CT, CT/PET and PET Imaging)

100 cm
Separation PET
CT PET CT
Access to
Patient

ADAC - A PHILIPS Medical Systems Company

High Performance Discovery PET-CT
Systems
Discovery LS16 Discovery ST4

Fixed &
Mobile

Discovery Systems… Advancing Cancer Care & Beyond

 REVEAL SCANNER FAMILY

REVEAL-XVI
Combined Performance
REVEAL-QS
Cost effective performance

REVEAL-RT REVEAL-XL
function + anatomy High throughput
 GSO Thermal Properties
Light output vs. Temperature

1 .4
• eases environmental
1 .3
constraints
R e la tiv e L ig h t O U tp u t

1 .2
1 .1
(air conditioning)
NaI • makes it the material
1
0 .9 GSO of choice for
0 .8 LSO combined PET/CT
0 .7 BGO tomographs
0 .6
0 10 20 30 40 50
T e m p e ra tu re (°C )
Moszynski et al. IEEE NS-45:
472-477, 1998

ADAC - A PHILIPS Medical Systems Company

 Attenuation Correction
(Strengths and Weaknesses)
• 137Cs Attenuation correction
+ Larger FOV (less truncation) 56 vs. 50 cm
+ Reduced organ motion artifacts
+ SUV capability validated
+ Improved arms down imaging
– Statistical noise higher than with CT

• CT Attenuation correction
– Breath hold acquisition
+ Reduced imaging time
• 22 min with CT attenuation correction
• 28 min. with 137Cs attenuation correction
– CT issues leading to noise or artifacts
• Extrapolation from 80 to 511 keV
• Motion: lung expansion, bowel, gas, …

ADAC - A PHILIPS Medical Systems Company

Ready to use synergies

“The use of PET

information in the
RT planning
process significantly
improves outcome
and patient
management.”
R. Thompson, M.D.
Cedars Sinai Medical Center,
Los Angeles, USA

ADAC - A PHILIPS Medical Systems Company

Gated FDG study showed that a much smaller area need be
irradiated than the larger area delineated by the green line, thus
sparing unnecessary irradiation of the spinal cord

Wagner H.N., “Highlights 2001 Lecture: Against All Odds, Nuclear Medicine
Has Thrived” J Nucl Med; Vol 42(8);12N-30N.
GE APPROACH: DISCOVERY ST

• BGO Crystals – improved technology

• Increasing size of opening
• Highest sensitivity per dose injected
GE APPROACH: DISCOVERY ST
GE APPROACH: DISCOVERY ST
 DETECTOR MATERIALS
Is LSO the future of PET?

For:
Ronald Nutt, Ph.D., CTI

Against:
Joel S. Karp, Ph.D., Philips

“Is LSO the Future of PET?” Controversies - Eur J Nucl Med 29(11);1523-25. 2002.
 FOR:
Ideal detector material in this order:

• High speed or faster decay time

• High light output
• High density
• Commercial production
• LSO very closely approaches ideal material

“Is LSO the Future of PET?” Controversies - Eur J Nucl Med 29(11);1523-25. 2002.
 Light output, decay time, and density for the
four PET detector materials

Characteristic LSO BGO GSO NaI

Light output (%) 75 15 25 100

Decay time (ns) 40 300 60 230
Density (g/cc) 7.4 7.1 6.8 3.7

“Is LSO the Future of PET?” Controversies - Eur J Nucl Med 29(11);1523-25. 2002
 IMPORTANCE OF LIGHT OUTPUT:

Determines amount of signal available to perform

the gamma ray positioning, energy discrimination
(or scatter rejection) and the time window
(establishes noise level resulting from random
events)

“Is LSO the Future of PET?” Controversies - Eur J Nucl Med 29(11);1523-25. 2002
 LSO PRODUCTION:
• Can produce up to 200 units/year
• Made animal research micro PET or PET/CT
events
• Panels 370 x 530 mm, 10,1080 crystals,
4 x 4 x 20 mm; 88 PMT
• 5 Panels continuous motion, hexagonal array,
closed gantry
• 700 mm aperture and 500 mm axial
• Sixth side holds 68Co / 68Ga point sources for
simultaneous emission / transmission
“Is LSO the Future of PET?” Controversies - Eur J Nucl Med 29(11);1523-25. 2002
 GSO PRODUCTION:

• Hitachi, Japan

• Not clear how fast they can produce

“Is LSO the Future of PET?” Controversies - Eur J Nucl Med 29(11);1523-25. 2002
 AGAINST:
Yes and No (if it is the only detector)
Best for 3D, for 2D it is hard to beat BGO

BGO: 3D:
Highest stopping power 5 times sensitivity
Not suitable for 3D Offset by gain in scatter
Poor energy resolution, & random coincidence
not important, stop Both decrease contrast
scatter and randoms To evaluate the trade off
measure NEC
It measures contribution
of scatter random to the
image even after correction
“Is LSO the Future of PET?” Controversies - Eur J Nucl Med 29(11);1523-25. 2002
 GSO:

• Developed in 1983, used in Karolinska Group

• Dropped interest after BGO

• Better energy resolution

“Is LSO the Future of PET?” Controversies - Eur J Nucl Med 29(11);1523-25. 2002
 SYSTEM ENERGY RESOLUTION:
• Depends on detector design and accuracy of system
wide calibrations
• Beta energy resolution is important especially with
3D PET. It allows the scanner to be operated with a
higher energy threshold E threshold closer to 511 keV
in order to reduce scatter and random coincidences
GSO LSO BGO
System E Resolution 15% 20% 20%
E Threshold keV 420 350 350

• Lower E threshold leads to higher scatter fraction

“Is LSO the Future of PET?” Controversies - Eur J Nucl Med 29(11);1523-25. 2002
GSO: LIGHT OUTPUT VARIATIONS:
( 7% MORE CONSISTENT WITH GSO )

• Not radioactive (although it does not interfere

with coincidence imaging)

• Does interfere with single acquisition for

transmission scanning

“Is LSO the Future of PET?” Controversies - Eur J Nucl Med 29(11);1523-25. 2002
 COST:
• Both GSO and LSO
5 – 10 higher than NaI
3 – 6 higher than BGO

• More production unlikely to reduce cost because

of higher melting paint > 2000°C and difficulty
in growing larger bowls

“Is LSO the Future of PET?” Controversies - Eur J Nucl Med 29(11);1523-25. 2002
 GSO DETECTOR DESIGN:
• Incorporates discrete crystal but with continuous
optical coupling through a light guide to (different
from blocks)
• 4 monocrystals, hexagonal assay, 39 PMT
• For each event a local cluster of seven PMT’s is
used to determine position and energy
• Continuous assay better because of less
differences in light collection between antas
and periphery
“Is LSO the Future of PET?” Controversies - Eur J Nucl Med 29(11);1523-25. 2002
 NEW DETECTOR MATERIALS:
• Mixed Lutelium silicate UTAR, Canada
• < GSO (90% Lutelium and 10% Gadolinium) Hitachi, Japan
• More promising:
• Lantharium Scintilators Sanit-Gobain ‘Crystals and detectors
• Fast decay time
• 3% energy resolution
• Lower stopping power
• < 100 ns pulse integration time
• Excellent rejection of scatter and randoms by using
Ethreda 470 keV and narrow time window and use
• High light output
• Excellent spatial resolution
• Low melting point ( 800°C)
• Cheaper production
“Is LSO the Future of PET?” Controversies - Eur J Nucl Med 29(11);1523-25. 2002
 PET THROUGHPUT
SURVEY RESULTS
Average Total Body Imaging Time

70 62

60
51
50
36
40
Minutes

30

20

10

0
Na(Tl) ADAC BGO - GE LSO -
C-PET Advance REVEAL-XL

Data provided by CPS Innovations and

IMV
 PET THROUGHPUT
SURVEY RESULTS
Maximum Patients/Day*
(8 hours/average imaging time)
13.1
14

12
9.4
10
Max # procedures

7.8
8

0
Na(Tl) ADAC BGO - GE LS O -
*Calculated based on average scan time C-PE T Adv a nc e REVEAL -XL
Data provided by CPS Innovations and
IMV
 IMAGING TIME
- DETAILED ANALYSIS
Average Dose (mCi) A v era g e # B e d Imaging time per # bed
T otal Body s tep s/T o ta l b o d y EM/T M
15 8
13.2 12.8 10
6.6
6.2
12 5.9
6 8 2.1
2.9
9
# step s
6

minutes
mCi

4
2.2
6 4.9 4
6.7
5.4
2 3.8
3 2

0 0 0
Na(Tl) BGO LSO N a(Tl) BGO LS O Na(Tl) BGO LSO
ADAC C- GE REVEAL- A D AC C- GE R EV EA L- ADAC C- GE REVEAL-
PET Advance XL P ET A dvance XL PET Advance XL

Note: C-PET specified max Note: 100% GE Advance collected in 2D

dose of 5mCi 100% REVEAL-XL / C-PET collected in 3D
Data provided by CPS Innovations and
IMV
 REVEALRT
Dependable Image Quality
7 minute exam 12 minute exam 17 minute exam

120 lbs – 1 min/bed 160 lbs - 2 min/bed 250 lbs - 3 min/bed

Images courtesy of UCLA, Dr. Czernin
 REVEALRT

3 min/bed, five beds, 1 min CT: 16 min total

Images courtesy of UCLA, Dr. Czernin

 REVEALRT

2 min/bed, five beds: 10 min total PET Acquisition

5 min/bed, five beds: 25 min total

Images courtesy of UCLA, Dr. Czernin
REVEALRT
Clinical Integration
 REVEALRT
Therapy Connectivity
• Therapy Connectivity
– PET and CT DICOM
– Established connectivity
with:
• Varian, Nomos, Nucletron
 REVEALRT
Therapy Positioning

• Therapy
Positioning with
Open-Port™ design
– MED-TEC flat
pallet and patient
positioning
accessories
• BreastBoard
• HipFix
• Type-S Headholder
 microPET Detector Technology

•Detector with electronics

•Etched LSO
Vs.
Un-etched LSO •Module and detector
components
 Whole Body Rat FDG Study

1.5mCi
.5mCi FDG,
6 bed positions,
20 min/position

microPET P4

Crump Institute for Molecular Imaging

 Pharmacokinetic Analysis

7000
Coronal slices Kidney Heart Liver Bladder
6000
through individual 5000
frames of the time 4000
Activity

lapse movie for the 3000

HSV-tk positive 2000

mouse 1000

0
0 500 1000 1500 2000 2500 3000
Time (sec)
 From Mouse to Man:
PET Imaging the Striatal Dopamine System
Human

Monkey

Rat

Mouse
[C-11]WIN
Binding
 CONCLUSION:

• It is rapidly moving technology

• Listen, watch, educate yourself,

use your own judgment

“Is LSO the Future of PET?” Controversies - Eur J Nucl Med 29(11);1523-25. 2002