SMALL ANIMAL IMAGING THE BRIDGE BETWEEN IN VITRO TECHNOLOGY AND PERSONALIZED MEDICINE Christian Vanhove (November 8, 2012)
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SMALL ANIMAL IMAGINGTHE BRIDGE BETWEEN IN VITRO TECHNOLOGY AND
PERSONALIZED MEDICINE
Christian Vanhove (November 8, 2012)
The evolution of bio-imaging
Weissleder and Pittet. Imaging in the era of molecular oncology. Nature 2008
The evolution of bio-imaging
Weissleder and Pittet. Imaging in the era of molecular oncology. Nature 2008
MRICTUS SPECT & PETRX
Medical imaging
The evolution of bio-imaging
Weissleder and Pittet. Imaging in the era of molecular oncology. Nature 2008
Microscopy & Optical imaging
The human eye can focus from 20cm to
infinity control illumination and resolve to
±100 m however it can’t magnify
The Nimrud Lens
Babylon750-710 BC
The British Museum
Molecular Biology
The ‘omics’ is very trendy today in daily science
Genomics
Proteomics
Metabolomics
Gene≠
Blueprint
Molecular Biology
DNA±25000 genes
mRNA±500000
ProteinsNx107
MetabolitesNx106
Transcription
Translation
Effect of the environment (life style)
Genomics
Proteomics
Metabolomics
The evolution of bio-imaging
Weissleder and Pittet. Imaging in the era of molecular oncology. Nature 2008
The Bridge
Molecular Biology Medical Imaging
Small Animal Imaging
The evolution of bio-imaging
Weissleder and Pittet. Imaging in the era of molecular oncology. Nature 2008
In the beginning there was …
Wilhelm RöntgenNobel Prize Physics 1901
Discovery of X-rays
22 December 1895Hand of Anna Berthe
23 January 1896Hand of Albert von Kölliker,
a famous anatomist
… the first medical image ?
The hand of a 12-year-old boy who had shot himself one month before his hand was examined by x-rays in 1896 at at Columbia University.
… the first medical image ?
The hand of a 12-year-old boy who had shot himself one month before his hand was examined by x-rays in 1896 at at Columbia University.
FightFindFollow
Up
Diagnosis Treatment Follow-up
The medical imaging timeline
Weissleder and Pittet. Imaging in the era of molecular oncology. Nature 2008
The medical imaging timeline
SPECT
X-ray
MRI
1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010
CT
PET
Fiber optics
The medical imaging timeline
SPECT
X-ray
MRI
1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010
CT
PET
Fiber optics
FightFindFollow
Up
Diagnosis Treatment Follow-up
Imaging Analogue
Imaging Analogue
Imaging Analogue
Imaging Analogue
Imaging Analogue
Imaging Analogue: Structural Imaging
How can we (as foreign investigators) get more information about Earth?
Imaging Analogue
How can we (as foreign investigators) get more information about Earth?
Imaging Analogue
Imaging Analogue
Imaging Analogue: Functional Imaging
Molecular InvestigatorContrast Agent
RadiotracerImaging Probe
Biomarker
Imaging Analogue: Functional imaging
Carrier or AgentSpecific moiety
Moiety for localization of specific process
Label Moiety for detectionMoiety for imaging signal
Imaging Analogue: Functional imaging
Micro-Macro-Structure-Function
Weissleder and Pittet. Imaging in the era of molecular oncology. Nature 2008
Micro-Macro-Structure-Function
An
ato
my
Fun
ctio
nal
Macroscopic Microscopic
Micro-Macro-Structure-Function
An
ato
my
Fun
ctio
nal
Macroscopic Microscopic
Structural versus Functional
Time / Course of disease
Sym
pto
ms
Functional changes
Clinical Symptoms
Anatomic imaging
Follow-upTreatment
Functional imaging
The importance of functional imaging
Why was this disease not earlier detected ?
The importance of functional imaging
100€1€ 100€1€
The importance of functional imagingMulti-modality imaging
The role of molecular biology
Genomics
Proteomics
Metabolomics
Cancer
Alzheimer
CAD
Biomarkers
The FDA defines a biomarker as, "A characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention".
Target
Agent
Optical label (in vitro)Radioactive label (in vivo)
Uses of biomarkers
Individualized/Personalized Medicine
Scientific Publications Biomarkers
MICAD
List contains today 5076 items !!Probably not complete
Only 236 FDA ApprovedFrom which 123 Discontinued
Thus 113 still available47 SPECT and PET Tracers
3357 SPECT and PET tracers(66%)
47 FDA Approved
R. Weissleder, B.D. Ross, A. Rehemtulla, S.G. Gambhir (Eds.), Molecular Imaging: Principles and Practice.
Biomarker development
Multi-disciplinary
R. Weissleder, B.D. Ross, A. Rehemtulla, S.G. Gambhir (Eds.), Molecular Imaging: Principles and Practice.
Biomarker development
In-v
itro
In-v
ivo
Biomarker developmentCellular / Molecular level Cell culture
Small animalHuman
Mo
lecu
lar
Bio
logy
Pre
clin
ical
imag
ing
Clin
ical
imag
ing
In-v
itro
In-v
ivo
Small animal imaging
70 kg 250 g
280x smaller in volume
±6.5 times smaller / direction
1 mm 150 µm
Small animal imaging
70 kg 20 g
3500x smaller in volume
±15 times smaller / direction
1 mm 66 µm
Small animal imaging
Bed Bench
!!! OpticalImaging !!!
Clinical – Human Pre-Clinical – Animal
Small animal imaging
Clinical – Human Pre-Clinical – Animal
Bed Bench
Translational imaging
!!! OpticalImaging !!!
Small animal imaging
Disease Progression
imaging
quantitative parameterstherapy
Response to Therapy
Modality Study time Resolution IntrinsicContrast
ProbeSensitivity
DynamicImaging
RadiationDose
Cost
SPECT 30-90 min 0.5-2 mm None <pM Yes 10-100cGy 700K
PET 5-60 min 1-2 mm None <pM Yes 10-100cGy 700K
MRI ±60 min <100 µm High µM - mM Yes - 1M
CT 10-15 min <200 µm Low mM No 10-20cGy 350K
US ±60 min <100 µm Low ? Yes - 200K
BLI ±5 min ±1 cm None nM Yes - 250K
FLI ±5 min <5 mm Variable nM No - 150K
NIR ±10 min <5 mm None pM No - 250K
Small animal imaging
Multi-modality imaging
Small animal imaging
Multi-dimensional imaging
Quantitative
In summary
Molecular Biology Medical Imaging
Small Animal Imaging
In summary
Anatomy / Structure
Physiology
Functional/Metabolism
Molecular/Cellular
Genomics/Proteomics
In summary
Anatomy / Structure
Physiology
Functional/Metabolism
Molecular/Cellular
Genomics/Proteomics
Imag
e-n
-om
ics
In summary
Small animal imaging
Multi-modality Multi-dimensional Multi-disciplinary
Multi-skilled
SMALL ANIMAL IMAGINGTHE BRIDGE BETWEEN IN VITRO TECHNOLOGY AND
PERSONALIZED MEDICINE
Christian Vanhove (November 8, 2012)
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