Download Prostate Cancer

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
index
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
Motivation
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
Prostate 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)
Tracers
PET tracers for prostate cancer
Tracer
Mechanism
Specificity
Uptake
Glucose metabolism
Non specific
Low uptake
Non specific
High uptake
Non specific
High uptake
Non specific
High uptake
Non specific
High uptake
[18F]FACBC
Non specific
High uptake
[18F]FLT
Non specific
Low uptake
Non specific
High uptake
Androgen receptor
Specific
High uptake
[18F]DCFBC, [18F]DCFPyL,
[68Ga]PSMA
PSMA inhibitor
Specific
High uptake
[64Cu/89Zr]J591, [89Zr]5A10,
others
Free PSA and PSMA
antibodies
Specific
High uptake
[18F]FDG
[11C/18F]choline
Lipid metabolism
[11C/18F]acetate
[18F]NaF
Calcium analog
[11C]methionine
Amino acid transport
Cell proliferation
[18F]FMAU
[18F]FDHT
PSMA tracers
Compound is inhibitor of
a specific site in PSMA
(high affinity):
It bounds strongly and
only to PSMA
Low molecular
(fast uptake)
weight
* 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
PSMA tracers
Ga68-PSMA
A.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 article
F18-choline
Ga68-PSMA
F18-PSMA
F18-PSMA
R.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
New prospects for PET
Vision
“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.
Typical patient path
Impact of Hi Res PET with highly specific tracer
diagnosis/staging:
•high resolution localization
inside prostate
•detection of early
metastasis in lymph nodes
high PSA
biopsy: high resolution
localization inside prostate
PET-guided
US-guided
biopsy
blind biopsy
X
false positive
X
over treatment
prostatectomy
PET negative
PET
PET positive
true positive
PET-aided
treatment
choice of
treatment
active
surveillance
true negative
no treatment
X
true negative
false negative
no treatment
under treatment
X
localized therapy: BrachyTP, RadioTP, Hadrons, HIFU
PET
monitoring
PET guidance for
surgery
accurate
monitoring with
PET
adjust therapy
High resolution, high sensitivity with new PET scanners
Improvements in PET technology in recent years:
•scintillation material: LSO (LYSO)
•small crystal detectors
•long axial coverage (>20cm)
•PSF reconstruction
•TOF reconstruction
•new modality:
osem 4mm
psf 2mm
-> higher sensitivity
-> higher resolution
-> higher sensitivity
-> lower noise, higher contrast
-> lower noise, faster convergence, better
localization accuracy
-> PET/MR
psf+tof 2mm
osem 2mm
osem+tof 2mm
PST+TOF: lower noise -> smaller pixel-size and better spatial resolution.
High resolution, high sensitivity with new PET scanners : a simulation
High resolution, high sensitivity with new PET scanners : a simulation
Original image
Resample
(2mm pixel)
Deconvolve
(pixel size & filter)
Forward project
into sinogram
New image
Apply normalization-1
& attenuation
reconstruct
Add Poisson noise
Add lesions
Scale to set counts
Add randoms
Add scatter
High resolution, high sensitivity with new PET scanners : a simulation
Lesions
Create lesions in two positions:
• inside the prostate (to differentiate
extra capsule and intra capsule
tumors)
• outside the prostate in the pelvic area
Lesions
(simulate metastasis on lymph
• Start from clinical 11C-choline images
nodes)
• Add lesions
• Lesion intensity: SUV = 4, 6, 8
• Lesion size: 4 mm, 6 mm, 10 mm
• Forward project, add simulated Scatter, Randoms, Poisson noise
• Total number of netTrues (Trues+Scatter) = 30x106
• Random Fraction=50%
• 100 or 50 realizations
Reconstruction
• Method 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)
High resolution, high sensitivity with new PET scanners : a simulation
11C-choline
patient with simulated small lesions: 6mm lesion, 6:1 contrast
(a)
(b)
(c)
(a) the original PET/CT image, with no simulated lesion;
(b) the simulation with lesions, reconstruction with low resolution OSEM;
(c) the simulation with lesions, PSF+TOF reconstruction with 2mm voxel size
Original reconstruction: OSEM, 5.5x5.5x3.3 mm3 voxels, 20 subsets, 2 iterations, 6mm filter
Proposed reconstruction: OSEM+PSF+TOF, 2x2x2 mm3, 21 subsets, 2 iterations, no filter
High resolution, high sensitivity with new PET scanners : a simulation
Numerical observer’s analysis
LROC curve for all data (all patients, all lesions)
Higher detectability with high resolution imaging
4mm lesion
6mm lesion
10mm lesion
PET + MR: multi parametric MRI
PET + MR: multi parametric MRI
PET + Multi parametric MR:
•T2w MRI
(anatomy)
•Dynamic Contrast Enhanced (DCE) MRI
•Diffusion Weighted Imaging (DWI) MRI
(vascularity)
(water diffusion, cell density)
•Magnetic Resonance Spectroscopy Imaging (MRSI)
(choline/citrate ratio,13C pyruvate/lactate ratio)
synergic contribution to diagnosis !
PET + MR: multi parametric MRI
DCE (Dynamic contrast enhanced MRI): Gd-chelate as contrast
agent for angiogenesis
S.Verna et al., “Overview of Dynamic Contrast-Enhanced MRI in Prostate Cancer Diagnosis
and Management”, AJR 198,1277–1288, 2012
T2w
fused
DCE
PET + MR: multi parametric MRI
DWI (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
MRSI: (choline+creatine)/citrate ratio as a marker of cancer
K.L.Zachian et al.,“1H magnetic resonance spectroscopy of prostate cancer: Biomarkers for
tumorcharacterization”, Cancer Biomarkers 4, 263-276, 2008
PET + MR: multi parametric MRI
MRSI: hyperpolarized 13C (13C-pyruvate contrast agent), tracks a
dramatic increase in lactate/pyruvate ratio in tumor cells
Simon Hu et al.,“13C-Pyruvate Imaging Reveals Alterations in Glycolysis that Precede c-MycInduced Tumor Formation and Regression”, Cell Metabolism 14, 131–142, 2011
Before
therapy
After
therapy
PET + MR: multi parametric MRI
PET+Multi parametric MR to guide the biopsy
11C-choline
PET/CT
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, 2012
PET/CT & PET/MR
T2w MRI + DWI MRI + DCE MRI
DWI
*Munich, on Siemens mMR
DCE
MultiPar-MR
PET/MR
T2w
New directions: PET scanner architectures for imaging of prostate cancer
New directions: PET scanner architectures for imaging of prostate cancer
Question: which approach is most interesting or effective or realistic ?
• 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 cancer
 Pros: available now, general purpose scanner
 Cons: 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 scanner
 Cons: engineering development, all cost is for urologist
New directions: instrumentation for biopsy
TASKS:
Detection and diagnosis
Staging and characterization
Surgery and biopsy
New directions: instrumentation for biopsy
Today, 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.
“on-line” MR guided biopsy
“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
New directions: more on biopsy
Question: which approach is best to guide a prostate cancer biopsy?
Method
performance:
sensitivity&localization
US
Poor: blind biopsy
on-line MR
High: can locate some tumors
MR+US (MR off-line,
registered)
PET+US (PET off-line,
registered)
Adequate: can locate some
tumors but possible registration
issues
Adequate+: can locate active
tumors but possible registration
issues
technical complexity
none
low
cost
Low
Moderate+: requires to
perform biopsy in MR scanner
low-moderate
Moderate: requires MR scan
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
“on-line” PET guided biopsy using magnification probes ?
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
Needs:
 High resolution, high sensitivity probe:
• Small crystals, TOF, magnification effect*
 Complex 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?
PET ring
from S. Majewski
*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, 2009
F. 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
Thanks!
Put on your pink glasses!
And thanks to:
Harshali Bal
Lars Eriksson
Hossein Jadvar
Peter Choyke
Stefano Fanti
Martin Pomper
Stan Majewski
It is a time of great opportunities for
PET imaging of prostate cancer!
H. 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)