1. 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
2 Department of Chemistry,
1 Department of Physics,
University of Massachusetts Boston, Boston, MA
This work is supported by UMass Boston and DF/HCC
NIH U54 Minority Institution/Cancer Center Partnership Grant-1U54CA156732/4

2. Outline Motivation Background Properties Bodipy derivatives PAZ-Scan
Data
Conclusion and future work

3. 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.

4. Background
Jablonski diagram

5. Background - the photoacoustic effect
LIGHT 
SOUND 
The photoacoustic effect (conversion of light into sound)
was published in 1880 by Alexander Graham Bell

6. Desired Physical Properties of MPACs
Strong light absorption (emax) in biological transparent window ( nm)
Large Stoke’s shift, dissipates excited state energy as heat (DH) via structural reorganization (DV)
A photoacoustic signal is basically a photoinduced heat + pressure wave

7. Desired Physical Properties of MPACs
Strong light absorption (emax) in biological transparent window ( nm)
Small Stoke’s shift, very sharp excitation and emission peak, high fluorescence quantum yield.
BODIPY
Large emax, tunable lmax
High Φf
How to re-direct excited state energy?
= Fluorescence Quenching

8. Tuning of BODIPY Photophysics
Absorption spectra
Emission spectra
Fc-absorption spectra

9. Optical Characterization of BODIPY Derivatives
Variations of BODIPY
UV-vis
(lmax, nm) ε
( M-1cm-1)
fwhm
( cm-1)
Emission
ΦFl
1-BODIPY
500
1.20
5.0
510
0.9
2-MeOPhBODIPY
568
0.88
4.0
580
3-(MeOPh)2BODIPY
640
1.17
2.9
654
0.4
4-FcBODIPY
594
0.89
0.75
n/a
5-Fc2BODIPY
685
1.10
1.0

10. PAZ-scan Experiment

11. 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

12. PA and Optical Response of BODIPY

13. PA and Optical Response of MeOPh-BODIPY
Both Linear and nonlinear absorption are occurring.

14. PA and Optical Response of MeOPh2-BODIPY
Both Linear and nonlinear absorption are occurring.

15. PA and Optical Response of Fc2-BODIPY

16. PA Response of Fc and MEOH2-BODIPYs
Reductive quenching
mechanism

17. PA and Fluorescence of MeOH2-BODIPY

18. 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.

19. Acknowledgement Dr. Jonathan Rochford Samir Laoui
Dr. Maryam Hatamimoslehabadi
Dr. Matthieu Fremette
Stephanie Bellinger-Buckley
U-54
The Graduate Student Association at Umass-Boston

20. Thank you for your attention!