Maurizio Conti Siemens Healthcare Molecular Imaging Knoxville Tennessee USA Mediterranean Thematic Workshops in Advanced Molecular Imaging Alghero September 27 2014 index motivation amp introduction ID: 785548
Download The PPT/PDF document "Prospects for imaging prostate cancer wi..." is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Prospects for imaging prostate cancer with PET/CT and PET/MR
Maurizio Conti
Siemens Healthcare Molecular Imaging, Knoxville, Tennessee, USA
Mediterranean Thematic Workshops in Advanced Molecular Imaging
Alghero
, September 2-7, 2014
Slide2index
motivation & introduction
PET tracers for prostate cancer
advances
in PET technology
and new opportunities for PET
improved detectability for prostate cancer lesions
PET/MR for prostate cancer imaging
new directions: a discussion on PET scanner architectures
new directions: guided biopsy
Slide3Motivation
Prostate cancer is the leading cancer for men in the US (and second for death):
one out of six men
will be diagnosed with prostate cancer in his life;
Accurate localization/staging is the key to success in treatment; The techniques available for detection and localization are very poor, compared to all other major cancers.
Typical prostate cancer path:High PSA“blind” biopsy (false negative 30% !)if positive, prostatectomy + bone scan for metastasis
future of PET in prostate cancer:
Develop high specificity tracers
Develop high performance PET instrumentation
Slide4Prostate cancer imaging
The holy grail(s) of prostate cancer imaging today:
Specific tracers, high sensitivity and high specificity of the imaging scan
Improve early detection
and localization of small lesion inside prostate and in lymph nodes (support for diagnosis and biopsy and treatment)assess aggressiveness of disease via non-invasive techniques (treatment or active surveillance)
Slide5Tracers
Slide6PET tracers for prostate cancer
Tracer
Mechanism
Specificity
Uptake
[
18
F]FDG
Glucose metabolism
Non specific
Low uptake
[
11
C/
18
F]choline
Lipid metabolism
Non specific
High uptake
[
11
C/
18
F]acetate
Non specific
High uptake
[
18
F]
NaF
Calcium analog
Non specific
High uptake
[
11
C]methionine
Amino acid transport
Non specific
High uptake
[
18
F]FACBC
Non specific
High uptake
[
18
F]FLT
Cell proliferation
Non specific
Low uptake
[
18
F]FMAU
Non specific
High uptake
[
18
F]FDHT
Androgen receptor
Specific
High uptake
[
18
F]DCFBC, [
18
F]
DCFPyL
, [
68
Ga]PSMA
PSMA inhibitor
Specific
High uptake
[
64
Cu/
89
Zr]J591, [
89
Zr]5A10, others
Free PSA and PSMA antibodies
Specific
High uptake
Slide7PSMA tracers
Compound is inhibitor of a specific site in PSMA (high affinity):
It bounds strongly and only to PSMA
Low molecular weight (fast uptake)
*
Banerjee et al.: “Synthesis and Evaluation of Technetium-99m- and Rhenium-Labeled Inhibitors of the Prostate-Specific Membrane Antigen (PSMA)”J Med Chem 51, 4504-4517, 2008
** Courtesy of Martin
Pomper
Slide8A.Afshar-Oromieh
et al.: “Comparison of PET imaging with a 68Ga-labelled PSMA ligand and 18F-choline-based PET/CT for the diagnosis of recurrent prostate cancer”, EJNMMI 41: 11-20 (2014)* Figure from journal articleR.C.Mease et al.: “N-[N-[(S)-1,3-Dicarboxypropyl]Carbamoyl]-4-[18F]Fluorobenzyl-LCysteine, [18F]DCFBC: A New Imaging Probe for Prostate Cancer”, Clin. Cancer Res. 14: 3036-3043 (2008)* Courtesy of Martin Pomper, private communication
PSMA tracers
Ga68-PSMA
F18-PSMA
F18-choline
Ga68-PSMA
F18-PSMA
Slide9New prospects for PET
Slide10“High sensitivity, high resolution PET with high specificity tracers, for early and spatially accurate detection of tumors inside the prostate.”
Objectives:
Better diagnosis and staging: providing a tool for guided biopsy and more accurate assessment of the grade of the disease;
Reduce the need for radical prostatectomy;
Guide the radical prostatectomy, obtaining less positive margins and sparing healthy tissue;Safer diagnosis and staging: reducing the need of "blind" surgical removal of pelvic lymph nodes;Provide more accurate tumor localization information for any localized therapy, in order to achieve more effective and safer therapy.
Vision
Slide11Typical patient path
high PSA
US-guided
blind biopsy
false positive
true positive
true negative
false negative
no treatment
under treatment
over treatment
treatment
active surveillance
prostatectomy
localized therapy:
BrachyTP, RadioTP, Hadrons, HIFU
monitoring
adjust therapy
PET
PET-guided
biopsy
X
X
PET
PET-aided choice of
treatment
PET positive
Impact of Hi Res PET with highly specific tracer
PET guidance for surgery
accurate monitoring with PET
true negative
no treatment
PET negative
X
X
diagnosis/staging:
high
resolution localization inside
prostate
detection of early metastasis in lymph nodes
biopsy: high
resolution localization inside
prostate
Slide12High resolution, high sensitivity with
new
PET scanners
Improvements in PET technology in recent years:
scintillation material: LSO (LYSO) -> higher sensitivitysmall crystal detectors -> higher resolutionlong axial coverage (>20cm) -> higher sensitivity
PSF reconstruction -> lower noise, higher contrastTOF reconstruction -> lower noise, faster convergence, better localization accuracynew modality: -> PET/MR PST+TOF: lower noise -> smaller pixel-size and better spatial resolution.
osem 4mm
psf 2mm
psf+tof 2mm
osem 2mm osem+tof 2mm
Slide13High resolution, high sensitivity with
new
PET
scanners : a simulation
Slide14Original image
Resample
(2mm pixel)
Deconvolve
(pixel size & filter)
Add lesions
Forward project into sinogram
Apply normalization
-1
& attenuation
Add scatter
Add randoms
Add Poisson noise
reconstruct
New image
Scale to set counts
High resolution, high sensitivity with
new
PET
scanners : a simulation
Slide15Lesions
Start from clinical
11
C-choline images
Add lesions Lesion intensity: SUV = 4, 6, 8Lesion size: 4 mm, 6 mm, 10 mmForward project, add simulated Scatter, Randoms, Poisson noiseTotal number of netTrues (Trues+Scatter) = 30x106Random Fraction=50%100 or 50 realizationsReconstructionMethod analog to original image for comparison (typically OSEM, 4mm pixel, 21 subsets, 2 iterations, 6mm filter)OSEM+PSF+TOF (2mm pixel, 21 subsets, 2 iterations, <4mm filter)
LesionsCreate lesions in two positions:inside the prostate (to differentiate extra capsule and intra capsule tumors)outside the prostate in the pelvic area (simulate metastasis on lymph nodes)
High resolution, high sensitivity with
new
PET
scanners : a simulation
Slide1611
C-choline patient with simulated small
lesions: 6mm
lesion, 6:1 contrast
the original PET/CT image, with no simulated lesion;
the simulation with lesions, reconstruction with low resolution OSEM;
the simulation with lesions, PSF+TOF reconstruction with 2mm voxel size
Original reconstruction: OSEM, 5.5x5.5x3.3 mm
3
voxels, 20 subsets, 2 iterations, 6mm filter
Proposed reconstruction: OSEM+PSF+TOF, 2x2x2 mm
3
, 21 subsets, 2 iterations, no filter
(a) (b) (c)
High resolution, high sensitivity with
new
PET
scanners : a simulation
Slide17LROC curve for all
data (all patients, all lesions)
Higher detectability with high resolution imaging
4mm lesion
6mm lesion
10mm lesion
Numerical observer’s analysis
High resolution, high sensitivity with
new
PET
scanners : a simulation
Slide18PET + MR: multi parametric MRI
Slide19PET + MR:
multi parametric MRI
PET + Multi parametric MR:
T2w MRI
(anatomy)
Dynamic Contrast Enhanced (DCE) MRI (vascularity)Diffusion Weighted Imaging (DWI) MRI (water diffusion, cell density)Magnetic Resonance Spectroscopy Imaging (MRSI) (choline/citrate ratio,13C pyruvate/lactate ratio)
synergic contribution to diagnosis !
Slide20DCE (Dynamic
contrast enhanced
MRI):
Gd
-chelate as contrast agent for angiogenesisS.Verna et al., “Overview of Dynamic Contrast-Enhanced MRI in Prostate Cancer Diagnosis and Management”, AJR 198,1277–1288, 2012
fusedDCE
T2w
PET + MR:
multi parametric MRI
Slide21DWI (Diffusion
weighted
MRI): restricted
water diffusion in tumor
B. Turbey et al., “Multiparametric 3T Prostate Magnetic Resonance Imaging to Detect Cancer: Histopathological Correlation Using Prostatectomy Specimens Processed in Customized Magnetic Resonance Imaging Based Molds”, Journal of Urology 186, 1818-1824, 2011
T2w
DWI
PET + MR:
multi parametric MRI
Slide22PET + MR:
multi parametric MRI
MRSI:
(
choline+creatine
)/citrate ratio as a marker of cancerK.L.Zachian et al.,“1H magnetic resonance spectroscopy of prostate cancer: Biomarkers for tumorcharacterization”, Cancer Biomarkers 4, 263-276, 2008
Slide23MRSI: hyperpolarized
13
C
(
13C-pyruvate contrast agent), tracks a dramatic increase in lactate/pyruvate ratio in tumor cellsSimon Hu et al.,“13C-Pyruvate Imaging Reveals Alterations in Glycolysis that Precede c-Myc-Induced Tumor Formation and Regression”, Cell Metabolism 14, 131–142, 2011
Before therapyAfter
therapy
PET + MR:
multi parametric MRI
Slide24PET+Multi
parametric MR to guide the biopsy
Takei et al., “
A
Case of Multimodality Multiparametric 11C-Choline PET/MR for Biopsy Targeting in Prior Biopsy-Negative Primary Prostate Cancer”, Clinical Nuclear Medicine 37, 918,
2012PET/CT
PET/MR
MultiPar-MR
11
C-choline PET/CT
&
PET/MR
T2w MRI + DWI MRI + DCE
MRI
*Munich, on Siemens
mMR
DWI
DCE
T2w
PET + MR:
multi parametric MRI
Slide25New directions: PET scanner architectures for imaging
of prostate cancer
Slide26Question: which approach is most interesting or
effective or realistic ?New directions: PET scanner architectures for imaging
of prostate cancer
a high performance whole
body PET scanner, with classic ring architecture, with top of the line reconstruction: high resolution, high sensitivity, PSF, TOF, optimized protocol for prostate cancerPros: available now, general purpose scannerCons: limited resolution (
4mm), limited sensitivity
the same high performance
whole body PET scanner
with
a high resolution
insert,
with a local
magnification;
Pros
: high res (≤2mm), can use present scanners
Cons
: technical issues, complex reconstruction
a
dedicated
high performance small
diameter PET camera with small scintillating
crystals, with increased sensitivity and resolution.
Pros
:
high
res
(≤
2mm), lower cost than full scannerCons: engineering development, all cost is for urologist
Slide27New directions: instrumentation for biopsy
TASKS:
Detection and diagnosis
Staging
and characterizationSurgery and biopsy
Slide28Today
, ultrasound, no information on the location of the tumor, only anatomical information of the shape of prostate
Future
, PET+CT/MR, high resolution information about
the location
of the tumor, fused with the anatomical map*.
* Even choline
could be used: low
specificity
but high sensitivity.
New directions: instrumentation for biopsy
Slide29“on-line” MR guided biopsy
Slide30“off-line” MR-US guided biopsy
Registration
method:
MR image is
acquired previously;MR volume is identified;MR-US are registered real time during US-guided biopsy.Rastinehad et al., “Improving Detection of Clinically Significant Prostate Cancer: Magnetic Resonance Imaging/Transrectal Ultrasound Fusion Guided Prostate Biopsy”, The Journal of Urology 191, 1749–1754, 2014 Commercial products: Koelis, UroNav, and Artemis
Slide31Question: which approach is
best to guide a prostate cancer biopsy?New directions: more on biopsy
Method
performance:
sensitivity&localizationtechnical complexitycostUS Poor: blind biopsynoneLow on-line MRHigh: can locate some tumors
lowModerate+: requires to perform biopsy in MR scannerMR+US (MR off-line, registered)Adequate: can locate some tumors but possible registration issueslow-moderateModerate: requires MR scanPET+US (PET off-line, registered)Adequate+: can locate active tumors but possible registration issues
low-moderate
Moderate: requires PET scan
MR+US (simultaneous)
High: can locate some tumors
moderate
Moderate+: requires to perform biopsy in MR scanner
PET+US (simultaneous)
High+: can locate active tumors
very high
High: requires to perform biopsy in PET scanner
MR+PET+US (simultaneous)
Very high: can locate active tumors
+ multimodality synergy
very high
Very high: requires
to perform biopsy in
PET/MR scanner
Slide32“on-line” PET guided biopsy using magnification probes ?
PET ring
from S.
Majewski
Simultaneous acquisition
method:biopsy probe in PET/MR or PET/CT scanner;US and/or PET and/or MR images are acquired simultaneously;the biopsy can be guided by US-PET-MR
*H
. Wu, Y.C. Tai et al.: “Micro Insert: A Prototype Full-Ring PET Device for Improving the Image Resolution of a Small-Animal PET Scanner”,
J Nucl Med 49, p. 1668,
2008
*J
.
Zhou,
J. Qi, “Theoretical analysis and simulation study of a high-resolution zoom-in PET system”,
Phys
Med
Biol 54, p. 5193, 2009F. Garibaldi et al.: “TOPEM
: A multimodality probe (PET TOF, MRI, and MRS) for diagnosis and follow up of prostate cancer” IEEE Nucl Sci Symp Conf Rec 2010, p. 2442, 2010
S.
Majewski
et al., “Dedicated mobile PET prostate imager”,
J
Nucl
Med 52 (Suppl. 1),
p.1945
,
2011
Needs:
High resolution, high sensitivity probe:
Small crystals, TOF, magnification
effect*
C
omplex reconstruction algorithm:
Localization of the probe
Attenuation
correction
Anisotropic resolution (artifacts?)
How to do an acceptable PET image in a few seconds?
High sensitivity and TOF?
Better reconstruction algorithms?
Slide33Thanks!
And thanks to:
Harshali Bal
Lars Eriksson
Hossein JadvarPeter ChoykeStefano FantiMartin PomperStan MajewskiH. Bal et al.,“Improving PET spatial resolution and detectability for prostate cancer imaging”, Phys. Med. Biol. 59, 4411-4426 (2014).M. Conti,“New prospects for PET in prostate cancer imaging: a physicist’s viewpoint”, Eur.J.Nucl.Med.Mol.Imag.Phys.,in press (2014)It is a time of great opportunities for PET imaging of prostate cancer!
Put on your pink glasses!