Transcript BODIPY Derivatives as Molecular Photoacoustic Contrast Agents

BODIPY Derivatives as
Molecular Photoacoustic Contrast Agents
Samir Laoui,1 Seema Bag,2 Olivier Dantiste,1 Mathieu Frenette,2 Maryam
Hatamimoslehabadi,1 Stephanie Bellinger-Buckley,2 Jen-Chieh Tseng,3
Jonathan Rochford,2 Chandra Yelleswarapu1
3Lurie
Family Imaging Center, Dana-Farber Cancer Institute, Boston, MA 02215.
2
Department of Chemistry,
1 Department of Physics,
University of Massachusetts Boston, Boston, MA 02125.
This work is supported by UMass Boston and DF/HCC
NIH U54 Minority Institution/Cancer Center Partnership Grant-1U54CA156732/4
Outline
•
•
•
•
•
•
•
Motivation
Background
Properties
Bodipy derivatives
PAZ-Scan
Data
Conclusion and future work
Motivation
• Photoacoustic imaging/tomography (PAI) is an in vivo, non-ionizing imaging
modality, that can provide location & metabolic activities of tumors with the
help of contrast agents.
• To date, a variety of near-infrared (NIR) absorbing fluorophores, e.g.
IRDye800CW, AlexaFluor 750 and ICG, have been used as exogenous contrast
agents for deep tissue imaging.
• Such contrast agents were originally designed for fluorescent imaging
applications and are thus optimized as such with a relatively poor photoacoustic
response, their only redeeming feature being their excellent optical absorption in
the biological transmission window of 600 – 1100 nm.
Jablonski diagram
N o rm alized A b so rp tio n -E m issio n
Background
0 .9
0 .6
0 .3
0 .0
400
500
W a v e le n g th (n m )
600
Background - the photoacoustic effect
LIGHT 
SOUND 
The photoacoustic effect (conversion of light into sound)
was published in 1880 by Alexander Graham Bell
Desired Physical Properties of MPACs
•
Strong light absorption (emax)
in
biological
transparent
window (650 - 950 nm)
•
Large
dissipates
Stoke’s
excited
shift,
state
energy as heat (DH) via
structural reorganization (DV)
 A photoacoustic signal is basically a photoinduced heat + pressure wave
Desired Physical Properties of MPACs
•
Strong light absorption (emax)
in
biological
transparent
window (650 - 950 nm)
•
Small Stoke’s shift, very
BODIPY
sharp excitation and emission
peak,
high
quantum yield.
fluorescence
Large emax, tunable lmax
High Φf
How to re-direct excited state energy?
= Fluorescence Quenching
Tuning of BODIPY Photophysics
F=0
1-BODIPY
2-MeOPh-BODIPY
3-(MeOPh)2-BODIPY
Relative Quantum Yield (FFl)
0.8
-1
-1
e (x 10 M cm )
1.0
5
0.6
0.4
0.2
0.0
200
300
400
500
600
700
Wavelength (nm)
Absorption spectra
800
900
1.0
1-BODIPY
2-MeO-BODIPY
3-(MeO)2-BODIPY
0.8
0.6
0.4
0.2
0.0
450
500
550
600
650
Wavelength (nm)
Emission spectra
700
750
Normalized Absorption
1.2
F=0
1.0
0.8
0.6
0.4
0.2
0.0
200
300
400
500
600
700
Wavelength (nm)
Fc-absorption spectra
800
900
Optical Characterization of BODIPY Derivatives
Variations of BODIPY
UV-vis
ε
fwhm
Emission
(lmax, nm)
M-1cm-1)
cm-1)
(lmax, nm)
(
(
ΦFl
1-BODIPY
500
1.20
5.0
510
0.9
2-MeOPhBODIPY
568
0.88
4.0
580
0.9
3-(MeOPh)2BODIPY
640
1.17
2.9
654
0.4
4-FcBODIPY
594
0.89
0.75
n/a
n/a
5-Fc2BODIPY
685
1.10
1.0
PAZ-scan Experiment
PAZ-scan Experiment
Nd:YAG Laser, 532 nm (or)
OPO laser, 680-980 nm
3 nsec pulse width
Ultrasound
transducer to
measure the
photoacoustic
signal
Fiber probe to
collect the
fluorescence signal
Optical detector
to measure the
transmitted
energy
PA and Optical Response of BODIPY
80
BODIPY
380
PA signal
375
40
370
365
20
PA signal
Optical
360
0
1E11
355
1E13
1E12
Intenstiy, J/m
2
Transmitted energy
60
PA and Optical Response of MeOPh-BODIPY
60
330
MeOPh BODIPY
Transmitted energy
329
PA signal
40
328
PA signal
327
Optical
20
326
0
1E11
325
1E13
1E12
2
Intensity, J/m
Both Linear and nonlinear absorption are occurring.
PA and Optical Response of MeOPh2-BODIPY
60
(MeOPh)2 BODIPY
345
Transmitted energy
340
PA signal
40
335
PA signal
Optical
20
330
1E11
325
1E13
1E12
2
Intensity, J/m
Both Linear and nonlinear absorption are occurring.
PA and Optical Response of Fc2-BODIPY
120
352
Fc2 BODIPY
100
Transmitted nergy
350
PA signal
80
348
60
346
40
PA Signal
20
0
1E11
344
Optical
342
1E13
1E12
2
Intensity, J/m
PA Response of Fc and MEOH2-BODIPYs
Photoacoustic signal (mV)
140
120
100
80
60
40
Reductive quenching
mechanism
20
0
0
1
2
3
12
Intenstiy (10 J m-2)
4
5
PA and Fluorescence of MeOH2-BODIPY
90000
Meoh2-BODIPY
85000
80000
10
PA Signal
75000
8
FL
PA Signal 70000
6
65000
60000
4
55000
2
50000
0
45000
1E9
1E10
Intensity Jm
-2
Fluorescence arb units
12
Conclusion
• Successfully engineered a PA response from the BODIPY chromophores.
• Fluorescence quantum yield has been reduced from 0.9 to ~0 and the absorbed
energy is channeled through non-radiative decay – increased in PA signal .
• Current work in progress is to move from using BODIPY derivatives to using
Curcumin derivatives.
Acknowledgement
•
•
•
•
•
•
•
Dr. Jonathan Rochford
Samir Laoui
Dr. Maryam Hatamimoslehabadi
Dr. Matthieu Fremette
Stephanie Bellinger-Buckley
U-54
The Graduate Student Association at Umass-Boston
Thank you for your attention!