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「物理・工学と高次生体イメージング技術開発計画」西本清一

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「物理・工学と高次生体イメージング技術開発計画」西本清一
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Physics, Engineering and Development Project
for Integrated Medical Bioimaging Technology
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Prologue
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Nanotechnology &Cancer
NCI Programs conducted over the past five
years have supported research on novel
Nanodevices that may
detect and pinpoint the location of
cancer at its earliest stages,
deriver anticancer drugs specifically to
malignant cells, and
determine in real-time if these drugs are
effective in killing malignant cells.
Sensitive, Fast, High-Resolution
Imaging Systems, Imaging Science
& Physics
Specific Molecular Targets
& Medicine
High Selective, Valid Probes
& Chemistry
AnatomyPhysiology
Metabolism
Molecular
CT
US
MRI
Nuclear
Optical
Nanosensor
CT-PET, CT-SPECT, PET-MRI
Radiology,2001,219:316
Message
Genomics
Gene
Single Nucleotide Polymophism
Structure
Function
Target
Number/cell
Gene (DNA)
Message
Protein
Function
2
50-1,000
100-1,000,000
massive
Proteomics
Metabolism &
Microenvironment:
Pathological Enzyme Activation,
pH, pO2 , Glucose, Cation,
Temperature, et al.
Radiology,2001,219:316
Nano-Bio Researches in Chemistry
DNA
45015%
45015%
2,10070%
J. Am. Chem. Soc., issues 1-48 (2004): 3,000
Tumor Vascular Markers
Tumor-Homing Peptide
c(CysAsnGlyArgCys) / c(CNGRC)
Tumor-Homing Phase
APN / CD13
overexpresses
along with
angiogenesis
• Fluorescence Probe • Antitumor Agent
CD13 Targeting
Fluorescence Imaging
Antitumor Prodrug
APN / CD13
13(*.-)
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Endothelial Cell
4+13
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Tumor Molecular Address
Corresponding Deliverer
Integrin avb3, avb5
ACDCRGDCFCG, RGD-4C
Aminopeptidase N ( CD13)
Cys-Asn-Gly-Arg-Cys
(CNGRC)
NG2
TAASGVRSMH
MMP-9
CTTHWGFTLC
NPY
NPY-peptide
Fmoc-Cys(A cm)-PEG-PS-Resin
i) 20%Piperidine
ii) Fomc-A mino A cid /HA TU /DIPEA
H2N-V ar-Cys(A cm)-A sn(Trt)-Gly-A rg(Pbf)-Cys(A cm)-PEG-PS-Resin
iii) I2 /DMF
iv) TFA /TIS/m-crosel/CH2Cl2
OH
O
O
H
N
H2N
NH
H
N
NH
O
HN
H
N
O
NH2
HN
S
S
O
NH2
O
O
FITC /DIPEA
OH
OH
O
O
H2N
H
N
NH
S
NH
H
N
O
HN
S
H
N
H
N
O
HN
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O
S
O
O
HO
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NH2
O
H
N
CNP01
CNP01 (FITC-VarCNGRC)
HT-1080 Cells (CD13+)
CNP01 (FITC-VarCNGRC)
MDA-MB-231 Cells (CD13–)
CNP03 (FITC-VarGGCRC)
Mismatch probe
HT-1080 Cells (CD13+)
CNP03 (FITC-VarGGCRC)
Mismatch probe
MDA-MB-231 Cells (CD13–)
Light On
Fluorescence
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HT-1080( CD13 + )
MDA-MB-231( CD13 - )
NGR-Qdot525
(ex = 480 nm)
NGR-Qdot705
(ex = 620 nm)
Fluorescent microscopic observation of HT-1080 cells (left) and MAD-MB-231 cells (right) as incubated
with 1 nM NGR-Qdot525 or NGR-Qdot705 for 3 hours at 37 °C and then washed with MEM .
5min
30min
1h
2h
4h
0.1 nmol/body
0.2 nmol/body
7h
1 day
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Org. Biomol. Chem., 2007, 5, 3745-3757
RSCPublishing
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Innovative Techno-Hub for Integrated Bioimaging
Vision & Mission
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