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Nuklearmedizinische Klinik im Klinikum rechts der Isarder Technischen Universität München
Molecular Imaging
As Tool for Personalized Medicine Markus SchwaigerTechnische Universität MünchenGermany
EC Conference European Perspective in Personalised Medicine Brussels 12-13 May 2011
Early Diagnosis and Risk Profiling Therapy Selection and Monitoring (Interv. and Pharm.)
Environment / Prevention (Life Style Modifications)
Gen Expr ProfileTissue arraysCell Genetic
Clinical DataFamiliy hx / Demographics
Environmental Risk Factors / Traetments
GenomicsSNPs
Genome-scale sequence
Proteomics Metabolomics
Serum and TissueBiomarkers
Molecular ImagingStructureFunction
Molecular Biology
Prediction
Molecular Medicine
What is Molecular Imaging?Non-invasive visualization of biologic and
cellular processes using molecular structures as imaging targets
InstrumentationImaging probes
What is Molecular Imaging?Non-invasive visualization of biologic and
cellular processes using molecular structures as imaging targets
InstrumentationImaging probes
Development of Imaging Technologies
Weissleder R, Pittet MJ; et al, Nature 2008, 580-589.
PET PET-CT
MRI
UltrasoundInterventional
Ultrasound
X-rays X-rays CT MSCT MSCT
LN-MRI Diffusion MRI
Diaphanoscopy Fibre optic FRI BLI HR-FRI Lifetime FRI
DOT FMT FPT FMT-CT FMT-MRI
MicroendoscopyMPMConfocalOCT,OFDIEpifluorescenceBright fieldBright field
Mic
ros
copy
Tom
ogra
phy
Mac
rosc
opi
cre
flect
anc
eX-
rays
an
d C
TU
ltras
oun
dM
R IP
E T
Clin
ical
pr
acti
ce
Opt
ical
de
velo
pme
nt
1900 1920 1940 1960 1970 1980 1985 1990 1995 2000 2001 2002 2003 2004 2005 2006 2007 2008 2010
MR PET Insert
Integrated MR/PET
0.03 kg0.30 kg
5.00 kg20.00 –
60.00 kg
Pre-clinical Clinical
3.00 kg
70.00 –150 kg
Courtesy National Research Institute-
OSKI- Hungary Brain Matters at Harbor-UCLA
National Cancer
Center-Japan
ErasmusMC, InsightMR I&
UNM, US
Courtesy UNM -US
From Animal to Humans
Translational Research
MR/PET München (TUM/LMU), Teil der DFG-Großgeräteinitiative
mMR- First MR/PET for Simultaneous WB -Imaging
MR/PET München (TUM/LMU), Teil der DFG-Großgeräteinitiative
Biograph mMR: Initial Results
Fürst et al8
MR/PET Workflow – Simultaneous Acquisition
Bed Position 1
Bed Position 2
Bed Position 3
Less than 30 mins for combined MR/PET Whole Body
Multi-Spectral Optoacoustic Tomography (MSOT)10-100micron resolution ● 5 – 30mm penetration
Institute for Biological & Medical Imaging (IBMI)
Multi-spectral illumination
Photon correction
Ultra wide-band acoustic detection
Spectral projection inversion (SPI)
IN: LIGHT OUT: SOUND
5 mm
6 mm
Ex-vivo histology / microscopy
mCherry expression
In-vivo MSOT
0.4mm 0.4mm
Nature Photonics 3, 412-417 (2009)
Intraoperative Imaging
Specific staining of CT26 tumors (d14)8h after i.v. injection of cmHsp70.1 mAb
Visible colors Fluorescence image (Cy5.5)
tumor
liverliver
tumor
32
Imaging Signals for Guidance of Interventions (Sugery/Endoscopy)
What is Molecular Imaging?Non-invasive visualization of biologic and
cellular processes using molecular structures as imaging targets
InstrumentationImaging probes
Cellular Stress
EnergyMetabolism
Proliferation
Perfusion
Metastasis
Angiogenesis
Hypoxia
Characterisation of Individual Tumor Biology Biologic Knowledge Imaging Tools
Molecular Imaging
Nuklearmedizinische Klinik im Klinikum rechts der Isar der Technischen Universität München
Hexokinase
no substrate for Phosphogluco-isomerase
Charged molecule → no passive diffusion
or cell membranepenetration
FURTHER GLYCOLYTICPATHWAY
no significant dephosphorylation
Imaging of Glucose MetabolismUptake and METABOLIC TRAPPING of [18F]FDG
OPO33-
F
OPO33-
F
Monitoring Therapy Response in Aggressive Lymphoma (DLBCL) by PET/CT
before therapy
after 6 x R-CHOP
Glucose Metabolism
Overall survival (intention-to-treat-analysis)Municon Trial
Median survival[95% CI] in months:
Metabolic Responder: Not reached
Metabolic Non-Responder:25.8 [19.4; 32.3]
Hazard ratio 2.13 [1.14-3.99]Log-rank p-value: p<0.015
Median follow-up: 28.0 monthsLancet Oncology 2007
Clinical Impact
Folkman J, N Engl J Med 1971
Therapeutic Targets
ANGIOGENESIS
OO
HOOH
NH
O
18F
OHNCO NH
NH
LysD-Phe
Asp
Gly
Arg
HO
OOO
HOOH
NH
O
18F
OHNCO NH
NH
LysD-Phe
Asp
Gly
Arg
HO
[18F]Galakto-RGDInhibitors of Angiogenesis
Therapeutic Target: Angiogenesis
Fusion of MR and RGD PET for Identification of Angiogenesis
C
FD
B
E
A
Avb3 Integrines
Combined analysis of αvβ3 expression, glucose metabolism and diffusivity with the Anima M3P software
T2w MRI ADC map and [18F]Galacto-RGD PET image fusion
DW-MRI: ADC map ADC map and [18F]FDG PETimage fusion
Cluster analysis of ADC and SUV of [18F]FDG PET
FDG
SU
V
ADC mm2/sec
Nekolla SG, van Marwick S 2010; Metz S, Beer AJ, JNM 2010;
MR/PET: translational research tool
Challenges for Clinical Application
Molecular imaging
Extraction of „Representative“ Signals Clinical Validation based on Outcome Clinical Acceptance and Reimbursement
• Biologic Specificity of Probes• Experimental Optimisation• Regulatory Hurdles• High cost to Clinical Product
Pathology of Alzheimer’s Disease
© National Institue of Aging
Clinical Translation
Mechanism of Amyloid Plaque ImagingTracers for Positron Emission Tomography (PET)
[11C]PIB
Vascularspace
NeuronGlial cell
Amyloid-Plaques
Molecular Imaging
Amyloid-Plaque Imaging (PET)
Glucose-metabolism
F-11 FDG30-60 min p.i.
AmyloidPlaque
ImagingC-11 6-0H-
BTA140-70 min
p.i.
M. Alzheimer Healthy ControlMCI
Surface projections, left lateral aspects
Amyloid-Plaques
Hypometabolism
Tailoring of TherapyEarlier Detectionof Disease
Longer Survival
Future of Molecular Imaging
Personalized Medicine
MR/PET München (TUM/LMU), Teil der DFG-Großgeräteinitiative
AcknowledgementsStephan NekollaSybille ZieglerAxel Martinez-MöllerSandra van Marwick
Hans Jürgen WesterSebastian FürstPetra Watzlowik
Gitti DzewasColetta KruschkeSylvia SchachoffPET- and Cyclotron-Team
Ambros BeerAlexander DrzezgaKen HerrmannMichael Souvatzoglou
Ernst J. RummenyMatthias EiberStephan Metz
Maximilian Reiser
Peter Bartenstein
Horst Kessler
Oliver Schnell
Markus NiemeyerMarion Kiechle