Size and lipid modification determine liposomal Indocyanine green performance for tumor imaging in a model of rectal cancer.
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ABSTRACT:
SUBMITTER: Bar-David S
PROVIDER: S-EPMC6561977 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Lymphatic vessels play a major role in cancer progression and in postsurgical lymphedema, and several new therapeutic approaches targeting lymphatics are currently being developed. Thus, there is a critical need for quantitative imaging methods to measure lymphatic flow. Indocyanine green (ICG) has been used for optical imaging of the lymphatic system, but it is unstable in solution and may rapidly enter venous capillaries after local injection. We developed a novel liposomal formulation of ICG (LP-ICG), resulting in vastly improved stability in solution and an increased fluorescence signal with a shift toward longer wavelength absorption and emission. When injected intradermally to mice, LP-ICG was specifically taken up by lymphatic vessels and allowed improved visualization of deep lymph nodes. In a genetic mouse model of lymphatic dysfunction, injection of LP-ICG showed no enhancement of draining lymph nodes and slower clearance from the injection site. In mice bearing B16 luciferase-expressing melanomas expressing vascular endothelial growth factor-C (VEGF-C), sequential near-IR imaging of intradermally injected LP-ICG enabled quantification of lymphatic flow. Increased flow through draining lymph nodes was observed in mice bearing VEGF-C-expressing tumors without metastases, whereas a decreased flow pattern was seen in mice with a higher lymph node tumor burden. This new method will likely facilitate quantitative studies of lymphatic function in preclinical investigations and may also have potential for imaging of lymphedema or improved sentinel lymph detection in cancer.
| S-EPMC3398157 | biostudies-literature
Project description:New high-resolution molecular and structural imaging strategies are needed to visualize high-risk plaques that are likely to cause acute myocardial infarction, because current diagnostic methods do not reliably identify at-risk subjects. Although molecular imaging agents are available for low-resolution detection of atherosclerosis in large arteries, a lack of imaging agents coupled to high-resolution modalities has limited molecular imaging of atherosclerosis in the smaller coronary arteries. Here, we have demonstrated that indocyanine green (ICG), a Food and Drug Administration-approved near-infrared fluorescence (NIRF)-emitting compound, targets atheromas within 20 min of injection and provides sufficient signal enhancement for in vivo detection of lipid-rich, inflamed, coronary-sized plaques in atherosclerotic rabbits. In vivo NIRF sensing was achieved with an intravascular wire in the aorta, a vessel of comparable caliber to human coronary arteries. Ex vivo fluorescence reflectance imaging showed high plaque target-to-background ratios in atheroma-bearing rabbits injected with ICG compared to atheroma-bearing rabbits injected with saline. In vitro studies using human macrophages established that ICG preferentially targets lipid-loaded macrophages. In an early clinical study of human atheroma specimens from four patients, we found that ICG colocalized with plaque macrophages and lipids. The atheroma-targeting capability of ICG has the potential to accelerate the clinical development of NIRF molecular imaging of high-risk plaques in humans.
| S-EPMC3112179 | biostudies-literature
Project description:ObjectiveDelineation of the intersegmental plane during pulmonary segmentectomy by systemic injection of indocyanine green (ICG) has been rapidly emerging. We evaluated the feasibility of the use of ICG in a large-scale cohort according to the type of segmentectomy and the presence of obstructive lung disorder and compared the demarcation status with air injection.MethodsWe collected the data of 209 patients who underwent segmentectomy using ICG at National Cancer Center Hospital, Tokyo, Japan. Data of the operation including the demarcation status of the intersegmental plane were analyzed retrospectively.ResultsThe median operation duration and blood loss were 105 minutes (interquartile range, 94-118 minutes) and 12 mL (interquartile range, 5-24 mL), respectively. Good demarcation of the intersegmental plane by ICG was observed in 184 (88.0%) cases, with no correlation to the type of resected segments or the presence of obstructive lung disorder. Postoperative complications of Clavien-Dindo classification grade 3 or more were observed in 5 cases (2.4%), and no ICG-related adverse event was noted. High-frequency jet ventilation was also used in 160 cases (76.6%) to delineate the intersegmental inflation-deflation plane. The air injected by high-frequency jet ventilation tended to spread further beyond the intersegmental plane that was depicted by ICG.ConclusionsThe use of ICG might demarcate the intersegmental plane more restricted to the target segment compared with air injection. Delineation of the intersegmental plane by ICG is feasible regardless of the type of segmentectomy or the presence of obstructive lung disorder, and it can be commonly applicable in pulmonary segmentectomy.
| S-EPMC8300924 | biostudies-literature
Project description:SignificanceExpanded use of fluorescence-guided surgery with devices approved for use with indocyanine green (ICG) has led to a range of commercial systems available. There is a compelling need to be able to independently characterize system performance and allow for cross-system comparisons.AimThe goal of this work is to expand on previous proposed fluorescence imaging standard designs to develop a long-term stable phantom that spectrally matches ICG characteristics and utilizes 3D printing technology for incorporating tissue-equivalent materials.ApproachA batch of test targets was created to assess ICG concentration sensitivity in the 0.3- to 1000-nM range, tissue-equivalent depth sensitivity down to 6 mm, and spatial resolution with a USAF test chart. Comparisons were completed with a range of systems that have significantly different imaging capabilities and applications, including the Li-Cor® Odyssey, Li-Cor® Pearl, PerkinElmer® Solaris, and Stryker® Spy Elite.ResultsImaging of the ICG-matching phantoms with all four commercially available systems showed the ability to benchmark system performance and allow for cross-system comparisons. The fluorescence tests were able to assess differences in the detectable concentrations of ICG with sensitivity differences >10× for preclinical and clinical systems. Furthermore, the tests successfully assessed system differences in the depth-signal decay rate, as well as resolution performance and image artifacts. The manufacturing variations, photostability, and mechanical design of the tests showed promise in providing long-term stable standards for fluorescence imaging.ConclusionsThe presented ICG-matching phantom provides a major step toward standardizing performance characterization and cross-system comparisons for devices approved for use with ICG. The developed hybrid manufacturing platform can incorporate long-term stable fluorescing agents with 3D printed tissue-equivalent material. Further, long-term testing of the phantom and refinements to the manufacturing process are necessary for future implementation as a widely adopted fluorescence imaging standard.
| S-EPMC7240319 | biostudies-literature
Project description:Fluorescence imaging in the second near-infrared window (NIR-II) holds promise for real-time deep tissue imaging. In this work, we investigated the NIR-II fluorescence properties of a liposomal formulation of indocyanine green (ICG), a FDA-approved dye that was recently shown to exhibit NIR-II fluorescence. Fluorescence spectra of liposomal-ICG were collected in phosphate-buffered saline (PBS) and plasma. Imaging studies in an Intralipid® phantom were performed to determine penetration depth. In vivo imaging studies were performed to test real-time visualization of vascular structures in the hind limb and intracranial regions. Free ICG, NIR-I imaging, and cross-sectional imaging modalities (MRI and CT) were used as comparators. Fluorescence spectra demonstrated the strong NIR-II fluorescence of liposomal-ICG, similar to free ICG in plasma. In vitro studies demonstrated superior performance of liposomal-ICG over free ICG for NIR-II imaging of deep (?4?mm) vascular mimicking structures. In vivo, NIR-II fluorescence imaging using liposomal-ICG resulted in significantly (p?<?0.05) higher contrast-to-noise ratio compared to free ICG for extended periods of time, allowing visualization of hind limb and intracranial vasculature for up to 4?hours post-injection. In vivo comparisons demonstrated higher vessel conspicuity with liposomal-ICG-enhanced NIR-II imaging compared to NIR-I imaging.
| S-EPMC6160486 | biostudies-other
Project description:The ability to switch optical imaging probes from the quenched (off) to the active state (on) has greatly improved target to background ratios. The optimal activation efficiency of an optical probe depends on complete quenching before activation and complete dequenching after activation. For instance, monoclonal antibody-indocyanine green (mAb-ICG) conjugates, which are promising agents for clinical translation, are normally quenched, but can be activated when bound to a cell surface receptor and internalized. However, the small fraction of commonly used ICG derivative (ICG-Sulfo-OSu) can bind noncovalently to its mAb and is, thus, gradually released from the mAb leading to relatively high background signal especially in the liver and the abdomen. In this study, we re-engineered a mAb-ICG conjugate, (Panitumumab-ICG) using bifunctional ICG derivatives (ICG-PEG4-Sulfo-OSu and ICG-PEG8-Sulfo-OSu) with short polyethylene glycol (PEG) linkers. Higher covalent binding (70-86%) was observed using the bifunctional ICG with short PEG linkers resulting in less in vivo noncovalent dissociation. Panitumumab-ICG conjugates with short PEG linkers were able to detect human epidermal growth factor receptor 1 (EGFR)-positive tumors with high tumor-to-background ratios (15.8 and 6.9 for EGFR positive tumor-to-negative tumor and tumor-to-liver ratios, respectively, at 3 d postinjection).
| S-EPMC3674550 | biostudies-literature
Project description:Indocyanine green (ICG) is one of the FDA-approved near infra-red fluorescent (NIRF) probes for cancer imaging and image-guided surgery in the clinical setting. However, the limitations of ICG include poor photostability, high concentration toxicity, short circulation time, and poor cancer cell specificity. To overcome these hurdles, we engineered a nanoconstruct composed of poly (vinyl pyrrolidone) (PVP)-indocyanine green that is cloaked self-assembled with tannic acid (termed as indocyanine green-based glow nanoparticles probe, ICG-Glow NPs) for the cancer cell/tissue-specific targeting. The self-assembled ICG-Glow NPs were confirmed by spherical nanoparticles formation (DLS and TEM) and spectral analyses. The NIRF imaging characteristic of ICG-Glow NPs was established by superior fluorescence counts on filter paper and chicken tissue. The ICG-Glow NPs exhibited excellent hemo and cellular compatibility with human red blood cells, kidney normal, pancreatic normal, and other cancer cell lines. An enhanced cancer-specific NIRF binding and imaging capability of ICG-Glow NPs was confirmed using different human cancer cell lines and human tumor tissues. Additionally, tumor-specific binding/accumulation of ICG-Glow NPs was confirmed in MDA-MB-231 xenograft mouse model. Collectively, these findings suggest that ICG-Glow NPs have great potential as a novel and safe NIRF imaging probe for cancer cell/tumor imaging. This can lead to a quicker cancer diagnosis facilitating precise disease detection and management.
| S-EPMC10161388 | biostudies-literature
Project description:BackgroundIn rectal cancer surgery, anastomotic leakage (AL) remains the most feared complication, with a frequency of up to 30% in non-high-volume centers. The preservation of proper vascularization is a key factor for successful anastomosis. The use of fluorescence with indocyanine green (ICG) as an intraoperative method to verify optimal perfusion is becoming an interesting tool in rectal surgery. Today, robotic surgery, together with the use of the intraoperative evaluation of the perfusion with ICG, could be a real strategy to deal with AL, allowing for a more delicate and less traumatic surgical technique. This strategy may allow for an extremely accurate surgery, and for optimal control of the proper vascularization of the rectum.MethodsThe purpose of this descriptive review is to analyze the impact of fluorescence and robotic surgery on short-term surgical outcomes for rectal cancer.ResultsWe performed a systematic literature search using the PubMed, Embase and Cochrane library databases. The primary endpoints were to evaluate the application of ICG fluorescence in robotic rectal surgery and the rate of anastomotic leakage when using these technological implementations. The secondary endpoints were to evaluate the dosage of ICG and the timing of application by different surgeons.ConclusionsICG fluorescence is an inexpensive and quick method to assess bowel perfusion, providing immediate feedback to the surgeon, even if its role has not been proven. A quantitative system must be systematically introduced to minimize the subjectiveness of the visualized image.
| S-EPMC9139806 | biostudies-literature
Project description:Recently, near-infrared (NIR) fluorescent dyes such as indocyanine green (ICG) have received tremendous interest as contrast agents for use in fluorescence-guided, intraoperative cancer resection surgery. However, despite showing great promise, ICG has many shortcomings such as rapid clearance and poor tumor accumulation. To improve the selective accumulation of ICG within tumors, numerous groups have formulated ICG into nanoparticles, but these approaches can suffer from rapid leakage of ICG, use of materials that exhibit poor or incomplete excretion, or complex chemistries that are not easily amenable to scale up for clinical use. Here, we developed a simple one-step method to prepare ICG-based fluorescent micelles that are composed solely of unmodified ICG and polycaprolactone (PCL), two clinically used materials with well-characterized safety profiles. The ICG-PCL micelles are prepared via oil-in-water emulsions, and the resulting micelles exhibit a uniform size, good reproducibility, and high loading efficiency. In vivo fluorescence imaging demonstrated that the ICG-PCL micelles led to a significant improvement in the accumulation and retention of ICG, in four different tumor models, compared with free dye, making them an attractive option for image-guided surgery.
| S-EPMC7245056 | biostudies-literature
Project description:Herein, a multifunctional traceable and ultrasound-responsive drug targeted delivery system based on indocyanine green (ICG) and folic acid (FA) covalently conjugated lipid microbubbles (ILMBs-FA) is proposed. After encapsulation of the anticancer drug resveratrol (RV), the composite (RILMBs-FA) with fluorescence and ultrasound imaging capacity was studied for highly sensitive dual-imaging guided tumor targeted therapy. The resulting RILMBs-FA with an average particle size of 1.32 ± 0.14 μm exhibited good stability and biocompatibility characteristics. The RILMBs-FA featured a high RV loading ratio and the encapsulated RV has been demonstrated to be released from the microbubbles triggered by ultrasound (US) waves. In addition, it was found that the linked FA could facilitate a high cellular uptake of RILMBs-FA via the FA receptor-mediated endocytosis pathway. Compared to free RV and RILMBs, RILMBs-FA with US irradiation demonstrated a more significant tumor cell-killing efficacy mediated by apoptosis in vitro. Eight hours post intravenous injection of RILMBs-FA, the composites showed maximum accumulation in tumorous tissues according to in vivo fluorescence and US images. This ultimately led to the best tumor inhibition effect among all tested drugs under US irradiation. In vivo biosafety evaluations showed that RILMBs-FA featured high biocompatibility characteristics and no significant systemic toxicity over the course of one month. Taken in concert, these results demonstrate the versatility of this drug delivery system with dual-imaging and ultrasound-triggered drug release characteristics for potential future applications in cancer theranostics.
| S-EPMC9086377 | biostudies-literature