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.

Background Jablonski diagram

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 Stoke’s shift, dissipates excited 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 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

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

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

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

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

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

PA and Optical Response of Fc2-BODIPY

PA Response of Fc and MEOH2-BODIPYs Reductive quenching mechanism

PA and Fluorescence of MeOH2-BODIPY

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

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