SIZE-TUNABLE ICG-BASED CONTRAST AGENT PLATFORM FOR TARGETED NEAR-INFRARED PHOTOACOUSTIC IMAGING

Author(s): Shrishti Singh, Giovanni Giammanco, Chih-Hsiang Hu, Joshua Bush, Leandro Soto Cordova, Dylan J Lawrence, Jeffrey L Moran, Parag V Chitnis, Remi Veneziano


Fig. 6. In vivo imaging using RGD-JAAZ particles. (A) Schematic and photograph of the 3D PAI acquisition on the TriTom™ imaging system. (B) Coronal and axial slabs of the baseline PA signal acquired at 895 nm. (C) Representative coronal and axial slabs of the ICG (left) and RGD-JAAZ particle (right) injections acquired at the peak excitation wavelength (i.e., 800 and 895 nm, respectively) over time. The displayed dynamic range for all images was set based on the baseline scan acquired at the same wavelength. (Legend): a. superficial thoracic vessels, b. liver c. spleen d. intestines e. thoracic vertebrae f. CuSO4 fiducial tube. (D) Axial slabs encompassing the iliac arteries (white ROI) used to calculate the achievable imaging depth for ICG and RGD-JAAZ particles 90-minutes post-injection. (E) Coronal slabs of oxyhemoglobin (red), deoxyhemoglobin (blue), and RGD-JAAZ particles (green) spectral unmixing overlaid on the 800 nm excitation scan of anatomy (white) at 0- and 90-minutes post-injection. Scale bars for all images are 10 mm. (n = 2 female nu/nu nude mice).

ABSTRACT

Near-infrared photoacoustic imaging (NIR-PAI) combines the advantages of optical and ultrasound imaging to provide anatomical and functional information of tissues with high resolution. Although NIR-PAI is promising, its widespread use is hindered by the limited availability of NIR contrast agents. J-aggregates (JA) made of indocyanine green dye (ICG) represents an attractive class of biocompatible contrast agents for PAI. Here, we present a facile synthesis method that combines ICG and ICG-azide dyes for producing contrast agents with tunable size down to 230 nm and direct functionalization with targeting moieties. The ICG-JA platform has a detectable PA signal in vitro that is two times stronger than whole blood and high photostability. The targeting ability of ICG-JA was measured in vitro using HeLa cells. The ICG-JA platform was then injected into mice and in vivo NIR-PAI showed enhanced visualization of liver and spleen for 90 min post-injection with a contrast-to-noise ratio of 2.42.

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Citation

S. Singh, G. Giammanco, C.-H. Hu, K. Bush, L. Soto Cordova, D. J. Lawrence, J. L. Moran, P. V. Chitnis, and R. Veneziano, “Size-tunable ICG-based contrast agent platform for targeted near-infrared photoacoustic imaging,” Photoacoustics, vol. 29, p. 100437, 2023/02/01/ 2023, doi: https://doi.org/10.1016/j.pacs.2022.100437.