Transcript Medical Imaging _AIME-SCMED2016x

Medical Imaging
Jordi Llop Roig
[email protected]
Madrid, November 24th 2016
INTRODUCTION – MEDICAL IMAGING
Image: Representation of something in 2 or more dimensions
Medical imaging: Acquire representations of “things” in 2 or more dimensions, in
order to provide relevant information about pathological processes
Anatomy
Function

US - Ecography
Gammagraphy

X-Ray
Positron Emission Tomography (PET)

Computerized tomography (CT)
Single Photon Emission Comp. Tomography (SPECT)

Magnetic Resonance Imaging (MRI)
fMRI, MRS
Optical Tomography
INTRODUCTION – MEDICAL IMAGING
Image: Representation of something in 2 or more dimensions
Medical imaging: Acquire representations of “things” in 2 or more dimensions, in
order to provide relevant information about pathological processes
Anatomy
Function

US - Ecography
Gammagraphy

X-Ray
Positron Emission Tomography (PET)

Computerized tomography (CT)
Single Photon Emission Comp. Tomography (SPECT)

Magnetic Resonance Imaging (MRI)
fMRI, MRS
Optical Tomography
INTRODUCTION – MEDICAL IMAGING
Image: Representation of something in 2 or more dimensions
Medical imaging: Acquire representations of “things” in 2 or more dimensions, in
order to provide relevant information about pathological processes
Anatomy
Function

US - Ecography
Gammagraphy

X-Ray
Positron Emission Tomography (PET)

Computerized tomography (CT)
Single Photon Emission Comp. Tomography (SPECT)

Magnetic Resonance Imaging (MRI)
fMRI, MRS
Optical Tomography
INTRODUCTION – MEDICAL IMAGING
INTRODUCTION – THE NEED FOR TRACKING
2007
2010
2008
INTRODUCTION – THE NEED FOR TRACKING
INTRODUCTION – THE NEED FOR TRACKING
GIRLFRIEND
PANTIES
INTRODUCTION – THE NEED FOR TRACKING
GIRLFRIEND
PANTIES
INTRODUCTION – THE NEED FOR TRACKING
molecule
GIRLFRIEND
PANTIES
radiolabelling
radiolabel
molecule
INTRODUCTION – THE NEED FOR TRACKING
+
SMALL MOLECULES
LARGE MOLECULES
INTRODUCTION – THE NEED FOR TRACKING
A
A
X
Z
Z
X
+ hn
SPECT
(R-g)
GAMMA EMITTER
A
X
Z
PET
A
Z+1
R-g
511 KeV
X
+
POSITRON EMITTER
POSITRON
R-g
511 KeV
INTRODUCTION – THE NEED FOR TRACKING
DETECTION OF 1 PHOTON
DETECTION OF 2 PHOTONS
EXAMPLES OF “MEDICAL IMAGING”
EXAMPLE 1: (INDIRECT) PROLIFERATION MARKER
Glucose
[18F]FDG
EXAMPLE 1: (INDIRECT) PROLIFERATION MARKER
Glucose
1. Trapping in SPE
2. Elution with K222/KHCO3
3. Solvent evaporation
18O(p,n)18F
EXAMPLE 1: (INDIRECT) PROLIFERATION MARKER
EXAMPLE 1: (INDIRECT) PROLIFERATION MARKER
EXAMPLE 1: (INDIRECT) PROLIFERATION MARKER
EXAMPLE 1: (INDIRECT) PROLIFERATION MARKER
Metabolic
trapping
EXAMPLE 1: (INDIRECT) PROLIFERATION MARKER
43-year-old man with metastasized medullar thyroid cancer
EXAMPLE 1: (INDIRECT) PROLIFERATION MARKER
43-year-old man with metastasized medullar thyroid cancer
BEFORE TREATMENT
EXAMPLE 1: (INDIRECT) PROLIFERATION MARKER
43-year-old man with metastasized medullar thyroid cancer
BEFORE TREATMENT
12 WEEKS
24 WEEKS
VANDETANIB
EXAMPLE 1: (INDIRECT) PROLIFERATION MARKER
43-year-old man with metastasized medullar thyroid cancer
3.0
SUV
2.5
% ID / g
2.0
1.5
1.0
0.5
0.0
0
2000
Time (s)
4000
METABOLIC CHANGES OCCUR BEFORE ANATOMICAL CHANGES !!!
6000
EXAMPLE 1: (INDIRECT) PROLIFERATION MARKER
Patient with a recurrence of cervical cancer
Lymph node
bone
EXAMPLE 1: (INDIRECT) PROLIFERATION MARKER
Patient with a recurrence of cervical cancer
Lymph node
Lymph node
bone
%ID / g
SUV
EXAMPLE 2: (INDIRECT) PROLIFERATION MARKER
EXAMPLE 2: (INDIRECT) PROLIFERATION MARKER
What if the tumour is in the brain?
[18F]FDG accumulates in the “healthy” brain
Low tumor-to-background ratio
BUT…
Amino acids also required by highly proliferating
cells
We need a labeled amino acid which is not
accumulated in “healthy” brain
EXAMPLE 2: (INDIRECT) PROLIFERATION MARKER
N2 / H2
14N(p,
α)11C
11CH
4
O
O
HO
HO
H NH2
H
H
SH
..
+
SH
..
11
C
H NH2 
H

O
H
H
I
+

S
11
H
O
C
I




HO
HO
H NH2
11
CH3 + HI
H NH2
S
11
CH
EXAMPLE 2: (INDIRECT) PROLIFERATION MARKER
Patient with glioblastoma in the right frontal lobe
CONTRAST ENHANCED MRI
[18F]FDG PET
[11C]METHIONINE PET
EXAMPLE 3: β-AMYLOID MARKERS
Alzheimer disease:
Neurodegenerative
Irreversible cognitive impairment / behavioral changes
Presence of Senile Plaques (β-Amyloid) and Neurofibrilary Tangles (NFTs).
O
O
S
H2N
HO
N
N
N
N
O
NH2
S
HO
O
EXAMPLE 3: β-AMYLOID MARKERS
Alzheimer disease:
Neurodegenerative
Irreversible cognitive impairment / behavioral changes
Presence of Senile Plaques (β-Amyloid) and Neurofibrilary Tangles (NFTs).
O
O
S
H2N
HO
N
N
N
N
O
NH2
SIMILAR STRUCTURE TO CONGO RED…
BUT SMALLER
S
HO
O
HO
S
11
CH3
NH
N
EXAMPLE 3: β-AMYLOID MARKERS
N2 / H2
14N(p,
α)11C
11CH
4
N
N
11
[ C]MeOTf, RT, 1 min
NH2
S
CH3
NH
ACN / Acetone
HO
11
HO
S
EXAMPLE 3: β-AMYLOID MARKERS
HC: Healthy control, 84 years old
AD: Alzheimer disease patient, 82 years old
AND MANY OTHERS…
[18F]F-
MAIN ADVANTAGES
Large number of molecular probes (many processes can be
investigated)
High sensitivity
Acceptable spatiotemporal resolution
Low amount of contrast agent required (First in Human)
Minimally invasive – longitudinal studies
Translational – from small rodents to large species to humans
WHAT ARE THE MAIN DRAWBACKS?
WHAT ARE THE MAIN DRAWBACKS?
CYCLOTRON
1 M€
25 Tm
VAULT
250 Tm
WHAT ARE THE MAIN DRAWBACKS?
HOT CELLS
200 K€
18Tm
SYNTEHSIZERS
300 K€
QC
200 K€
WHAT ARE THE MAIN DRAWBACKS?
150 m2
WHAT ARE THE MAIN DRAWBACKS?
Personnel
QP
QP (II)
Production Manager
Technicians
WHAT ARE THE MAIN DRAWBACKS?
WHAT ARE THE MAIN DRAWBACKS?
Is there any chance for a new
PET scenario?
[11C]COL
[18F]FDOPA
[11C]MET
[18F]FDG
WHAT ARE THE MAIN DRAWBACKS?
TAKE HOME MESSAGE
In vivo (nuclear) imaging can provide relevant medical information:
diagnosis, evaluation of the response to a treatment.
Other applications are mainly in the context of drug development.
Production of radionuclides is only the first step in the long process of
Medical Imaging.
Medical Imaging
Jordi Llop Roig
[email protected]
Madrid, November 24th 2016