iminds the conference: christian vanhove

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

MRICTUS SPECT & PETRX

Medical imaging

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 Bridge

Molecular Biology Medical Imaging

Small Animal Imaging

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



SPECT

X-ray

MRI

1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010

CT

PET

Fiber optics


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: Structural Imaging

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


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


70 kg 20 g

3500x smaller in volume

±15 times smaller / direction

1 mm 66 µm


Bed Bench

!!! OpticalImaging !!!

Clinical – Human Pre-Clinical – Animal


Clinical – Human Pre-Clinical – Animal

Bed Bench

Translational imaging

!!! OpticalImaging !!!


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


Multi-modality 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


Multi-modality Multi-dimensional Multi-disciplinary

Multi-skilled

SMALL ANIMAL IMAGINGTHE BRIDGE BETWEEN IN VITRO TECHNOLOGY AND

PERSONALIZED MEDICINE

Christian Vanhove (November 8, 2012)

iminds the conference: christian vanhove

Technology