What is the mechanism of action of indocyanine green (ICG)?

From the Guidelines

Indocyanine green (ICG) works by absorbing light in the near-infrared spectrum and emitting fluorescence at slightly longer wavelengths, allowing for real-time visualization of vascular structures, tissue perfusion, and lymphatic drainage. The mechanism of action of ICG relies on its ability to bind to plasma proteins, particularly albumin, after intravenous administration, which confines it to the vascular compartment 1. The dye is then exclusively taken up by hepatocytes and excreted unchanged into bile without undergoing enterohepatic recirculation. Some key points about ICG include:

• ICG achieves its tumor-targeting through “second window imaging,” which is based on the enhanced permeability and retention (EPR) effect 1
• ICG is a non-specific agent that is rapidly cleared by the liver and excreted in bile 1
• The standard dosage ranges from 0.1-0.5 mg/kg for most applications, with a maximum daily dose of 5 mg/kg
• ICG has an excellent safety profile with minimal toxicity due to its rapid clearance, though rare allergic reactions can occur, particularly in patients with iodine sensitivity since ICG contains iodine ICG clearance test is also used to assess liver function by calculating ICG retention (ICGR) in the liver after 15 min (ICGR15) 1. Key aspects of ICG in liver function assessment include:
• ICGR15 above 15–20% is indicative of impaired hepatic functional reserve 1
• Various cut-offs of ICG R15 can be part of the decision making algorithm for liver resective procedures in cirrhotic patients, limiting resection and segmentectomy to patients with ICG R15 below 20–25% and 30–35%, respectively 1

From the FDA Drug Label

Following intravenous injection, IC‑GREEN™ is rapidly bound to plasma protein, of which albumin is the principle carrier (95%). IC‑GREEN™ undergoes no significant extrahepatic or enterohepatic circulation; simultaneous arterial and venous blood estimations have shown negligible renal, peripheral, lung or cerebro‑spinal uptake of the dye. IC‑GREEN is taken up from the plasma almost exclusively by the hepatic parenchymal cells and is secreted entirely into the bile. The mechanism of action of indocyanine green (ICG) is based on its rapid binding to plasma protein, primarily albumin, and its subsequent exclusive uptake by hepatic parenchymal cells. The key points of its mechanism are:

• Binding to albumin: ICG is bound to plasma protein, with albumin being the primary carrier.
• Hepatic uptake: ICG is taken up almost exclusively by the hepatic parenchymal cells.
• Biliary secretion: ICG is secreted entirely into the bile. This makes ICG a helpful index of hepatic function 2.

From the Research

Mechanism of Action of Indocyanine Green (ICG)

• Indocyanine green (ICG) is a fluorescent dye that binds to albumin and lipoproteins in the blood, which affects its distribution and fluorescence properties 3.
• The binding of ICG to plasma proteins, particularly high-density lipoprotein (HDL) and low-density lipoprotein (LDL), influences its vascular and tissue permeability 3.
• ICG is used for intraoperative visualization of liver segments, bile ducts, and tumors, as well as for fluorescence angiography to visualize choroidal vessels 4, 5.
• The dye can be administered intravenously, and its fluorescence can be detected using special equipment, allowing for real-time visualization of structures and tissues 4, 6.

Properties of Indocyanine Green

• ICG has a high affinity for phospholipids, which are common molecular components of HDL and LDL 3.
• The absorption spectrum of ICG depends on the nature of the solvent medium and the dye concentration, with binding to plasma proteins causing a shift in the absorption spectrum 7.
• ICG solutions do not follow Lambert-Beer's law above 15 mg/L in plasma due to progressive aggregate formation with increasing concentration 7.

Clinical Applications of Indocyanine Green

• ICG is used in hepatic surgery to evaluate liver perfusion, function, and the biliary tree, as well as to visualize tumors and anatomical structures 4, 6.
• The dye can help detect small radiographically occult tumors, distinguish between cirrhotic nodules and cancer, and identify necrotic tumors in chemotherapy-damaged livers 6.
• ICG has a small learning curve, is minimally invasive, and can be used with special monitors and equipment, making it a safe and versatile method for anatomic liver mapping and tumor visualization 6.