Indocyanine Green (ICG, tradenames such as Indocyanine Green for Injection, USP and Verdye) has a well-documented high safety and tolerability profile[i] . Combined with its unique pharmacokinetic and photo physical properties Indocyanine Green, ICG enjoys wide acceptance and is used routinely in fluorescence guided procedures around the world.
There have been questions relating to iodine/iodide allergies, which require clarification. The ICG molecule itself does not contain the ion iodide. However, sodium iodide is added as part of the manufacturing process to lyophilize the ICG, which makes the product more stable and easier to dissolve.
Because your body does not produce iodine, it needs to be supplied in the diet. When iodine intake is poor, the body cannot produce enough thyroid hormones which can lead to hypothyroidism and goitre. Sodium iodide is found in iodized nutrients e.g. in fish. In fact, salt iodization is recommended in iodine-deficient regions.[ii]
The connection between an iodine/iodide allergy and ICG has been previously raised, however such a reaction is not considered plausible as the human body needs to absorb iodide and so allergic reactions based on sodium iodide, as contained in ICG powder, are not possible.
Allergies are reactions by the body to antigens. Antigens must fulfil certain criteria to induce antibody production and a subsequent allergy and one such criteria is the molecular size. Sodium iodide is a very small molecule which cannot be identified by the body as an antigen. Patients with an “allergy to iodine” react to macro molecules containing iodine/iodide, such as contrast media for x-ray, iodine-containing disinfectants and iodine-containing drugs like amiodarone. Unlike ICG, in these examples, iodide is bound within larger molecules.
A patient with a known allergy to macromolecular iodide/iodine containing compounds will not be at risk of an allergic reaction to ICG where the salt sodium iodide is incorporated.
A diagnostic application of Indocyanine Green, ICG means a total dose of up to 840μg of iodide can be administered. This may pose a risk for patients suffering from hyperthyroidism. In these patients ICG should only be used with caution or not administered at all.
Expert opinion of Prof. Dr. Med. R. Hehrmann, Department of Endocrinology, Medical Director,
Diakonie Krankenhaus, Stuttgart, Germany
[i] Alander JT, Kaartinen I, Laakso A, Pätilä T, Spillmann T, Tuchin VV, Venermo M, Välisuo P (2012) A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging 2012:940585
[ii] Elizabeth N Pearce, John H Lazarus, Rodrigo Moreno-Reyes, Michael B Zimmermann, Consequences of iodine deficiency and excess in pregnant women: an overview of current knowns and unknowns, The American Journal of Clinical Nutrition, Volume 104, Issue suppl_3, September 2016, Pages 918S–923S, https://doi.org/10.3945/ajcn.115.110429