General Description

Fluorescein sodium, also called uranine, has been commonly used as a quantitative fluorophore for studying different tissues of the eye. Its fluorescence, even at very low concentrations, makes it a useful tracer. [1]Its 560 nm wavelength light is detected as an intense yellow-green signal. Initially used for retinography, it became progressively essential for neurovascular procedures. The signal was significantly better with fluorescein sodium fluorescence than with Indocyanine green.[2]As a highly fluorescent molecule[3], it was widely used as a diagnostic reagent in ophthalmology. Fluorescein eye drops are effective for diagnosis of dry eye, abrasion of cornea, ulcer, corneal herpes, etc. Fluorescein contrast agent is used for discrimination of age-related macular degeneration, diabetic retinopathy, intraocular inflammation and the like.[7] Fluorescein sodium is the most suitable for corneal staining. Use of fluorescein sodium has the advantages of not causing discomfort or stinging, wide commercial availability, and ease of use because the cobalt blue exciter filter is mounted on many slit lamps.[4]Whats more, the use of fluorescein in glioblastoma resection can improve rates of tumor resection. [3]

Figure 1 Fluorescein Sodium powder

Pharmacokinetics

The pharmacokinetics of fluorescein are favorable for intraoperative use, with rapid distribution to tissues within 10 minutes, a plasma half-life of 23.5 minutes, and overall systemic clearance of 500 mg of fluorescein in 2 to 3 days.After intravenous administration, fluorescein sodium fluorescence can be visualized utilizing a surgical microscope equipped with a fluorescent filter system. Accordingly, the application of fluorescein sodium to resection of contrast-enhancing lesions in the quadrigeminal plate may confirm the surgical site, confirm acquisition of pathologic tissue, and guide resection.[3]

Preparation

1g of commercially available fluorescein sodium reagent was added to 2 mL of special grade ethanol (concentration 99.5% by volume) and stirred and dissolved over 1 hour, 1.4 mL of water was added and heated to 75°C. did. After adding 10mL of special grade 2-propanol (concentration 99.7% by volume), it was stirred and cooled to 12°C. over about 18 hours. The precipitated solid was subjected to solid-liquid separation under reduced pressure, and washed three times with 1mL of special grade 2-propanol. The obtained wet solid was dried under reduced pressure at 80°C to obtain pharmaceutical grade fluorescein sodium (crystalline form A, yield 35.7%).[7]

Side Effects

Fluorescein sodium injection can cause the side effects of varying severity, mostly minor side effects such as nausea , vomiting , sneezing , itchy skin and rash, itchy throat and cough, a transient palpitation and chest tightness, dizziness, chest tightness, fatigue and cold sweat. However, indications and contraindications should be strictly controlled and preparation for severe side effects should be ready during treatment to ensure patient safety in case of emergency.[5]Pure fluorescein sodium is considered relatively non-toxic. Toxic side effects are usually caused by impurities.[6]

Application

Fluorescein sodium is used in ophthalmic samples to produce fluorescein angiograms.Therefore, the development of sensitive and selective sensors for Fluorescein sodium ions is of high interest. Fluorescein sodium is shown to occur as singly and doubly charged anions in alkaline medium and both its forms a complex with polyvinyl pyrrolidone. Anthracene nanoparticles stabilized and capped by polyvinyl pyrrolidone undergo a binding interaction with fluorescein sodium, if present in close proximity.[1]Fluorescein sodium is a fluorescent tracer used for retinal and neurosurgical angiography. Due to fluorescein sodium fluorescence with higher Transcutaneous signal, Intraluminal visualization was possible with fluorescein sodium coloration during lymphaticovenular anastomoses. No adverse reaction occurred. The use of fluorescence microscope-integrated lymphangiography with fluorescein sodium may be superior to ICG fluorescence in assistance of lymphaticovenular anastomoses.[2]

Recent evidence suggests the safe application of fluorescein sodium in malignant glioma and can be applied to lesions of the tectal plate, where safe entry and identification of the gliotic plane are necessary. Furthermore, fluorescein-stained tissue was consistent with neurosurgical navigation, and provided the surgical team with intraoperative microsurgical guidance during tumor resection. This minimized normal tissue manipulation, and facilitated microsurgical dissection of the lesion from the surrounding parenchyma.Fluorescein staining was found by the operating surgeons to be advantageous during the course of the surgery, and provided intraoperative identification of residual tumor tissue. Utilizing a microsurgical mirror, identification of residual fluorescent tissue within the resection cavity facilitated complete resection and was verified on postoperative MRI.[3]

References

[1]Bhopate DP, et al. Polyvinyl pyrrolidone capped fluorescent anthracene nanoparticles for sensing fluorescein sodium in aqueous solution and analytical application for ophthalmic samples[J]. Luminescence.2015, 30(7): 1055-1063.

[2]Ayestaray B, Bekara F. Fluorescein sodium fluorescence microscope‐integrated lymphangiography for lymphatic supermicrosurgery[J]. Microsurgery. 2015, 35(5): 407-410.

[3]Ung TH, Kellner C, Neira J A, et al. The use of fluorescein sodium in the biopsy and gross-total resection of a tectal plate glioma[J]. Journal of Neurosurgery: Pediatrics, 2015, 16(6): 732-735.

[4]Eom Y, Lee HK, et al. Comparison of conjunctival staining between lissamine green and yellow filtered fluorescein sodium[J]. Canadian Journal of Ophthalmology, 2015, 50(4): 273-277.

[5]Shu-Hua Zhang, et al.Clinical observation of side effects of fluorescein sodium injection in fundus fluorescein angiography[J].Guoji Yanke Zazhi. 2013.

[6]Ogoshi K, Serup J. Safety of sodium fluorescein for in vivo study of skin[J]. Skin Research and Technology.2006, 12(3): 155-161.

[7] Ohno, Atsushi, et al. Method for purifying high-purity fluorescein sodium[P].WO 2017082430. 2017,05,18.