Measuring the fluorescent quantum efficiency of indocyanine green. Indocyanine green icg is a watersoluble tricarbocyanine dye with substantial absorption and fluorescence in the nearinfrared region nir 15,16. Effects of serum and physiological temperature on absorption and. A human photoacoustic imaging reporter gene using the. Fr2934954a1 fluorescent emulsion of indocyanine green. It also relates to a method of preparation and the use of this formulation. Read quantum yield of triplet formation for indocyanine green, journal of photochemistry and photobiology a. Indocyanine green incorporating nanoparticles for cancer theranostics.
The purpose of this paper is to give an overview of the recent surgical intraoperational applications of indocyanine green fluorescence imaging methods, the basics of the technology, and instrumentation used. The high transmission of the bandpass filters guarantees the brightest possible images, while the deep blocking ensures no unwanted light gets to the detector. The united states food and drug administration fda 17 has approved icg for use in diagnostic applications in clinical settings including its use as an optical contrast agent in the. S 1 t 1, by s 1 t 1 intersystemcrossing are determined for indocyanine green in dmso.
While measuring the absolute quantum yield of ire1050 using an integrating sphere, we found a lower value 0. Indocyanine green icg is a fluorescent dye that has been used for the imaging of retinal and choroidal vasculatures for more than 30 years. Since hepatoblastomas hbs possess similar features to hepatocellular carcinoma, fluorescenceguided surgery can be used for hbs, as aggressive surgical resection, even for distant metastases of hbs, often contributes positively. Indocyanine greenincorporating nanoparticles for cancer. Nearinfrared fluorescence enhance nirfe molecular imaging. Here, we show that two commercially available dyes with peak emission in the nir spectral region, including the fdaapproved contrast agent icg, can function as swir emitters. Jaggregates, indocyanine green, liposomes, theranostics, photothermal therapy introduction indocyanine green icg is a nearinfrared nir fluorescent dye marketed as icgreen, and has been clinically applied for angiography examination, sentinel lymph node mapping, and intraoperative imaging 1. Yield of fluorescence from indocyanine green in plasma and. Indocyanine green, known as icg, has been approved of clinical usage since 1956 3,4, used dominantly in angiography from about ten years after its approval. Shortwave infrared fluorescence imaging with the clinically.
Pai reporter genes would allow for monitoring of cell and gene therapies, but current reporters have immunogenicity andor toxicity concerns that may limit clinical translation. The optimum fluorescein concentration for the 100 pm cell was 1 g 11 2. Because of their unique configurations, fluorophores also have different excitation and emission spectrums. Pairedagent fluorescence molecular imaging of sentinel lymph. Indocyanine green icg is an fdaapproved nearinfrared fluorescent dye that has been used in. Fluorescenceguided surgery with indocyanine green icg for malignant hepatic tumors has been gaining more attention with technical advancements. Icg dye was developed for near infrared nir photography by the kodak research laboratories in 1955 and was approved for clinical use in 1959 by the fda. Application of this dye is limited by its numerous disadvantageous properties in aqueous solution, including its concentrationdependent aggregation, poor aqueous stability in vitro and low quantum yield. Icg absorbs red light about 740800nm 16 and emits fluorescent light peaking at 830nm in blood and 820nm in aqueous solution 1719. Despite the low quantum yield of the molecule, icg remains the hall. Wu d, xue d, zhou j, wang y, feng z, xu j, lin h, qian j, cai x.
Indocyanine green is a sterile, anionic, watersoluble but relatively hydrophobic, tricarbocyanine molecule with a molecular mass of 776 daltons. Absorption spectra, fluorescence quantum distributions, fluorescence quantum yields and degrees of fluorescence polarization vs. Interactions of indocyanine green and lipid in enhancing. Comparative study of the optical and heat generation. Pdf indocyanine green icg remains as the only near infrared dye approved by the fda.
Additionally, icg is highly bound to nonspecific plasma proteins, leading to. Recently, we demonstrated that icg dye has voltagesensitive properties with a dualcomponent. Applications in medicine indocyanine green icg is commonly used for vascular studies, and is one of few dyes used in. Apr 24, 2018 here, we show that indocyanine green, a clinically approved nearir dye, exhibits a remarkable amount of swir emission, which enables stateoftheart swir imaging with direct translation potential into clinical settings, and even outperforms other commercially available swir emitters.
The absorbance and nirii fluorescence emission of icg were. The properties of indocyanine green icg enable the observation of fluorescence images with a photodynamic eye pde system after icg is injected into a subject locally or intravenously. The measurement of fluorescence quantum yields can often be difficult and troublesome. May 01, 2016 its properties in blood and aqueous solution are thoroughly investigated by many studies. Indocyanine greenbased fluorescent angiography in breast. Rationally assembled albuminindocyanine green nanocomplex. We present results of a fluorescent quantum efficiency.
In 1 case report, anaphylactoid reactions with various manifestations occurred in 4 of 43 9. Indocyanine green fda prescribing information, side effects. The study confirms that the binding of icg with the bind sits on the albumin will result in improved. However, icg has several drawbacks such as aqueous instability, photodegradation, and low fluorescence quantum yield 2. The fluorescence quantum distribution of the indocyanine green j aggregates was studied by continuous wave laser excitation at 834 nm. Indocyanine green icg is a cyanine dye used in medical diagnostics. While the clinical fluorescenceguided surgery fgs field has been focused predominantly on indocyanine green icg imaging, there is accelerated development of more specific molecular tracers. Effects of serum and physiological temperature on absorption and fluorescence characteristics. Indocyanine green fluorescence in second nearinfrared nirii. Sorry, we are unable to provide the full text but you may find it at the following locations. For example, the ir800 dye with a peak emission wavelength of 800 nm exhibits a 10% quantum yield,21 and the indocyanine green icg dye exhibits only 4. Fluorescence properties and metabolic features of indocyanine. Fluorescent property of indocyanine green icg rubber ring. Experimental selective choriocapillaris photothrombosis.
Clinical applications of indocyanine green icg enhanced. In addition to the surgical applications, other recent medical applications of icg are briefly examined. The quantum yield of icg in the various solvents was measured relative to sodium fluorescein in distilled water. In vitro and in vivo characterization of a new micellar. Spectral characteristics of voltagesensitive indocyanine. This in vivo study assessed and compared the effectiveness of an aqueous indocyanine green icg formulation ricg and a lipid icg formulation licg in occluding the rabbit choriocapillaris, and determined the singlet oxygen quantum yields and aggregation properties of both formulations in vitro. Indocyanine green fda prescribing information, side. The yield of fluorescence from blood was investigated for various shear rates, concentrations of icg, and layer thicknesses. Extrahepatic cholangiography in nearinfrared ii window with the clinically approved fluorescence agent indocyanine green. Jan 01, 2020 indocyanine green for injection usp is a sterile, lyophilized green powder containing 25 mg of indocyanine green with no more than 5% sodium iodide.
Indocyanine green icg is the only nearinfrared nir fluorescent dye which is approved for medical applications. Absorption and fluorescence spectroscopic investigation of. In other words the quantum yield gives the probability of the excited state being deactivated by fluorescence rather than by another, nonradiative mechanism. Our techspec fluorescence filter sets are designed to provide brilliant images when integrated into a fluorescence microscope.
Fluorescence spectroscopic analysis of indocyanine green j. Photoacoustic imaging pai combines optical contrast with the resolution and depthdetection of ultrasound and is increasingly being utilized for medical imaging in patients. The monomer fluorescence quantum yield is limited to a few per cent by internal conversion. The fluorescence peak coincides with the absorption peak no stokes shift. Indocyanine green icg fluorescent dye has been approved by the fda for use in medical diagnostics. Indocyanine green should be used with caution in patients with renal failure or uremia, and those who are on dialysis. For medical diagnosis, icg is limited by its aqueous instability, concentrationdependent aggregation, and rapid degradation. Fluorescent property of indocyanine green icg rubber. Pairedagent fluorescence molecular imaging of sentinel. In addition to the surgical applications, other recent medical applications of icg are.
Fabrication of indocyanine green and 2h, 3hperfluoropentane. Fluorescence properties of indocyanine green as related to. The fluorescence spectrum was measured as a function of dye concentration in human whole blood and a few other common solvents in order to determine what fluorescence properties are unique to indocyanine green in blood. Icg photodegradation, through the oxidative cleavage of the polymethine chain, remained ivyspring. Indocyanine green fluorescence in second nearinfrared nir. Indocyanine green fluorescence in second nearinfrared. To prepare single doses, the icg stock solution was diluted with phosphatebuffered saline pbs to. To overcome the problems, many commercial nearir dyes, such as the nearir alexa fluor dyes, dylight dyes and irdyes, are prepared by placing a number of negatively charged sulfonate group on the dyes. Its high molecular weight, specific metabolic features. Laurence3, andrew gogbashian3, giuliano mariani4, and john v. It was recently reported that the wellknown and widely used fluorescent dye indocyanine green icg, which has fda approval, exhibits voltage sensitivity in various. Icgs long clinical usage verified many advantageous characteristics such as safety, good snr signal to noise ratio, short lifetime and cheapness 6. This indocyanine green price guide is based on using the. Ic green is a sterile, lyophilized green powder containing 25 mg of indocyanine green with no more than 5 % sodium iodide.
Indocyanine green in water forms j aggregates, which are observed as a redshifted narrow absorption band at 890 nm. Haolu wang 1, xinxing li 2, brian wanchi tse 3, haotian yang 1,4, camilla a. Stabilization of indocyanine green by encapsulation within. Indocyanine green prices, coupons and patient assistance programs. Their relative quantum yield measurements rely on a. Ic green indocyanine green for injection, usp sterile description. The fluorescence quantum yield is the ratio of photons absorbed to photons emitted through fluorescence. The fluorescence quantum yield of icg changes when the. Interactions of indocyanine green and lipid in enhancing near. Indocyanine green is a member of the miscellaneous diagnostic dyes drug class and is commonly used for diagnosis and investigation. F study on the encapsulation of the nearinfrared dye indocyanine green icg in bioresorbable. Indocyanine green icg is a fluorescence dye that is widely used for nearinfrared imaging.
Indocyanine green icg is widely used in medical imaging and testing. Differential transport function of lymphatic vessels in. Research open access highly enhanced optical properties. Chemistry on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
Liposometemplated indocyanine green j aggregates for near. Indocyanine green icg, a fda approved near infrared nir. Measurements were performedin vitro on samples of human blood in a coneplate shear chamber using frontal. Jan 31, 2019 following icg administration, cells synthetically expressing oatp1b3 exhibited significantly increased pai signals compared to control cells both in vitro and in mice. Several benefits of this technology are the human derivation of oatp1b3, and the high extinction coefficient, low quantum yield and preexisting clinical approval of icg. Its use in molecular imaging probes is limited because it loses fluorescence after binding to nonspecific plasma proteins, leading to rapid elimination from the body with a halflife of 2 4 min. Fluorescent angiography fa is a realtime imaging modality where an intravenous dyenamely, fluorescein and indocyanine green icgfluoresces and emits infrared energy upon excitation by a light source 11,12. The present invention relates to a formulation of indocyanine green in the form of a nanoemulsion, comprising a continuous aqueous phase and at least one dispersed oily phase, in which the oily phase comprises indocyanine green, at least one amphiphilic lipid and at least one solubilizing lipid. Indocyanine green fluorescence properties springerlink. Icgreen indocyanine green for injection, usp sterile description. Indocyanine green icg is a nearinfrared nir contrast agent commonly used for in vivo cardiovascular and eye imaging.
Fluorescence imaging is a method of realtime molecular tracking in vivo that has enabled many clinical technologies. Indocyanine green icg is a widely used nearinfrared nir tricarbocyanine fluorescent dye 1. Icgreen is a sterile, lyophilized green powder containing 25 mg of indocyanine green with no more than 5 % sodium iodide. Indocyanine green for injection usp is a sterile, lyophilized green powder containing 25 mg of indocyanine green with no more than 5% sodium iodide. We show that proximity of icg to a metallic silver particle increases its intensity approximately 20fold and decreases the decay time. Cancers free fulltext fluorescenceguided surgery for. Despite its long history of usage in clinical medicine, a systematic study of the effects of serum proteins at physiologically relevant levels and temperature on absorption and fluorescence characteristics of icg has been missing.
It enables the assessment of blood flow and tissue perfusion in preoperative, intraoperative, and postoperative setting. In 1958, icg was approved by fda for the use in indicatordilution studies in humans, and it is also one of the least toxic agents ever administered to humans, with the only known adverse reaction being rare. The fluorescent emission of ir820 has a lower quantum yield than icg but less dependence of the emission peak location on concentration. Quantum yield of triplet formation for indocyanine green. Voltagesensitive fluorescence of indocyanine green in the. Indocyanine green icg remains as the only near infrared dye approved by the fda. Liposometemplated indocyanine green j aggregates for. Fluorescence properties of indocyanine green as related to angiography. It is packaged with an aqueous solvent consisting of sterile water for injection used to dissolve the indocyanine green. While sulfonation improves dye solubility and fluorescence quantum yield to some. Extrahepatic cholangiography in nearinfrared ii window. Organic alternatives to quantum dots for intraoperative. The purpose of this work was to obtain more quantitative knowledge about the yield of fluorescence from retinal vessles during indocyanine green angiography icg. Indocyanine green icg, a fda approved near infrared nir fluorescent agent, is used in the clinic for a variety of applications including lymphangiography, intraoperative lymph node identification, tumor imaging, superficial vascular imaging, and marking ischemic tissues.
Application of this dye is limited due to its numerous disadvantageous properties in aqueous solution, including its concentrationdependent aggregation, poor stability and low quantum yield 1. To overcome these limitations, scientists have formulated icg in various liposomes, which are spherical lipid membrane vesicles with an aqueous core. Since its approval by the food and drug administration fda in the 1950s 2, icg has been clinically used in intraoperative angiography for assessment of superficial vessels in the. Indocyanine green for injection usp contains sodium iodide and should be used with caution in patients who have a history of allergy to iodides because of the risk of anaphylaxis.
It was recently reported that the wellknown and widely used fluorescent dye indocyanine green icg, which has fda approval, exhibits voltage sensitivity in various tissues, thus raising. Thorling 1, yuxin liu 5, margaux touraud 6, jean batiste chouane 6, xin liu 1, michael s. Since hepatoblastomas hbs possess similar features to hepatocellular carcinoma, fluorescenceguided surgery can be used for hbs, as aggressive surgical resection, even for distant metastases of hbs, often contributes positively to r0 complete. Herein, a novel phototheranostic nanocomplex that is selfassembled from bovine serum albumin bsa and indocyanine green icg is developed for enhanced nearinfrared nir fluorescence imaging, which benefits the guidance on in vivo cancer photothermal therapy ptt. Extrahepatic cholangiography in nearinfrared ii window with. Organic alternatives to quantum dots for intraoperative nearinfrared fluorescent sentinel lymph node mapping shunsuke ohnishi1, stephen j. The quantum yields have been corrected for the spectral response of the apparatus. Frangioni1 1beth israel deaconess medical center, boston, ma, 2general electric corporation, niskayuna, ny, 3brigham and womens hospital. Request pdf measuring the fluorescent quantum efficiency of indocyanine green encapsulated in nanocomposite particulates we present. Its complex spectral behavior and low quantum yield limits some applications.