Indocyanine green dye based bimodal contrast agent tested by photoacoustic/fluorescence tomography setup

Abstract

Multimodal imaging systems are in high demand for preclinical research, experimental medicine, and clinical practice. Combinations of photoacoustic technology with other modalities including fluorescence, ultrasound, MRI, OCT have been already applied in feasibility studies. Nevertheless, only the combination of photoacoustics with ultrasound in a single setup is commercially available now. A combination of photoacoustics and fluorescence is another compelling approach because those two modalities naturally complement each other. Here, we presented a bimodal contrast agent based on the indocyanine green dye (ICG) as a single signalling compound embedded in the biocompatible and biodegradable polymer shell. We demonstrate its remarkable characteristics by imaging using a commercial photoacoustic/fluorescence tomography system (TriTom, PhotoSound Technologies). It was shown that photoacoustic signal of the particles depends on the amount of dye loaded into the shell, while fluorescence signal depends on the total amount of dye per particle. For the first time to our knowledge, a commercial bimodal photoacoustic/fluorescence setup was used for characterization of ICG doped polymer particles. Additionally, we conducted cell toxicity studies for these particles as well as studied biodistribution over time in vivo and ex vivo using fluorescent imaging. The obtained results suggest a potential for the application of biocompatible and biodegradable bimodal contrast agents as well as the integrated photoacoustic/fluorescence imaging system for preclinical and clinical studies.

Multimodal Contrast Agents for Optoacoustic Brain Imaging in Small Animals

“…Many NIR II OA/fluorescence probes, such as novel NIR II OA probes with DNA-based nanocarriers, PEGylated Au nanoparticles, and SPNs, that are of high chemical stability, low toxicity, and a high signal-to-noise ratio showed great promise for multimodal imaging and photothermal therapy ( Jin et al, 2010 ; Ding et al, 2019 ; Meng et al, 2019 ; Sun et al, 2019 ; Zhang et al, 2019c ; Feng et al, 2020 ; Xu et al, 2020 ; Joseph et al, 2021 ; Miyasato et al, 2021 ). 5) Toward clinical translation: For fluorescence imaging, the U.S. Food and Drug Administration (FDA) approved several probes such as ICG ( Mokrousov et al, 2021 ), methylene blue, fluorescein, Prussian blue, 5-aminolevulinic acid ( Stummer et al, 2006 ), and Evans blue. A few fluorescence imaging contrast agents are in clinical trials at different 0stages including ONM-100 (pH-activable NP), second window ICG or SWIG, BLZ-100, Tumor Paint™, TumorGlow™, ABY-029, LUM015, SMG-101, OTL38, and Cornell dots ( Phillips et al, 2014 ; Whitley et al, 2016 ; Gutowski et al, 2017 ; Randall et al, 2019 ; Samkoe et al, 2019 ; Wahsner et al, 2019 ; Voskuil et al, 2020 ; Teng et al, 2021 ).…”

“…5) Toward clinical translation: For fluorescence imaging, the U.S. Food and Drug Administration (FDA) approved several probes such as ICG ( Mokrousov et al, 2021 ), methylene blue, fluorescein, Prussian blue, 5-aminolevulinic acid ( Stummer et al, 2006 ), and Evans blue. A few fluorescence imaging contrast agents are in clinical trials at different 0stages including ONM-100 (pH-activable NP), second window ICG or SWIG, BLZ-100, Tumor Paint™, TumorGlow™, ABY-029, LUM015, SMG-101, OTL38, and Cornell dots ( Phillips et al, 2014 ; Whitley et al, 2016 ; Gutowski et al, 2017 ; Randall et al, 2019 ; Samkoe et al, 2019 ; Wahsner et al, 2019 ; Voskuil et al, 2020 ; Teng et al, 2021 ).…”

“…Many chemical dyes for OA imaging have fluorescence properties and have been widely used in hybrid OA/fluorescence imaging ( Li et al, 2021a ); the OA/fluorescence dye ideally has a distinct absorption peak and a relatively low quantum yield to allow OA detection, for example, IRDye 800CW ( Attia et al, 2016 ) and naphthalocyanine ( Bézière and Ntziachristos, 2015 ), indocyanine green (ICG) ( Mokrousov et al, 2021 ), and Prussian blue. Administration of ICG visualizes blood vessels and enables OA/fluorescence imaging of cerebral perfusion in glioblastoma mouse models ( Burton et al, 2013 ).…”

A SERS platform based on diatomite modified by gold nanoparticles using a combination of layer-by-layer assembly and a freezing-induced loading method

“…In this work, we fabricated gold-coated diatomite composites using for the first time the combination of a recently developed freezing-induced loading (FIL) technique [59][60][61][62] and LbL assembly. [63][64][65][66][67] These techniques allowed us to obtain different coverages of diatomite by gold nanoparticles, depending on the number of layers.…”

Carbon Nanotube Microscale Fiber Grid as an Advanced Calibration System for Multispectral Optoacoustic Imaging

“…Another group of researchers used an agar phantom with 10 μm black-colored polystyrene spheres as a calibration system . One more study describes plastic tubes with an inner diameter of about 800 μm filled with ICG-based nanostructured contrast agents . However, among all the described methods, only one allows the verification of the real resolution of Raster-Scanning Optoacoustic Mesoscopy (RSOM) that is nearly 10–20 μm, and there is always a problem making the calibration system resistant to photobleaching, small enough for spatial resolution evaluation, and efficient at absorbing light coloring agent usually applied to fill voids in calibration systems.…”