March 2016

Iohexol — a CT scan contrast agent compound containing iodine

David Cash, PhD, Mohawk College (retired), Hamilton ON,

Introduction

ER doctor: We want a CT scan. You will be receiving an intravenous CT contrast agent.

Patient: What is the CT contrast agent?

ER doctor: Iohexol.¹

Iohexol is an organic compound containing iodine, an element that is chemically essential for human life.¹ In this context, it is a physical property of iodine that is important.

CT Scanner.

CT Scanner, Siemen Biograph By Brudersohn (http://creativecommons.org/licenses/by-sa/3.0), via Wikimedia Commons.

CT contrast agents

Contrast agents for CT (Computed Tomography) scanning¹ are radiopaque materials; usually a chemical compound containing either the element iodine or the element barium.¹ Iohexol is one of a group of iodinated organic compounds used for this purpose, all of which have the same central 1,3,5-triiodobenzene ring plus several water-soluble functionalities. These organic compounds all combine a relatively large mass of iodine into a single, water-soluble molecule. This results in a CT contrast agent whose aqueous solution has a relatively low osmotic pressure as expressed by its osmolality value.¹ The osmotic pressure is the pressure required to achieve osmotic equilibrium.

The contrast agent solution is usually delivered rapidly by injection, most often intravenously. The dosage may be relatively large, up to 60+ mL. Side effects are minimized, by keeping the osmolality of the solution as low as possible, although it will be significantly greater than that of body fluids. Contrast (image quality) is enhanced, by delivering as much contrast material as possible, in as small a volume as possible. Basically the goal is to achieve as high of a concentration of contrast agent as possible (better image) with as low of an osmotic pressure as possible (less toxicity).

Iohexol

Iohexol is produced and sold² by GE Healthcare,³ which manufactures and sells CT scanners and the associated software and pharmaceuticals. The structure and the IUPAC name of iohexol below are abstracted from its Wikipedia article.¹ Iohexol is very soluble in water; the most concentrated solution used being Omnipaque™ 350 which contains 75.5 % w/v in water and has 350 mg of iodine per mL. The osmolality of this solution, measured experimentally by vapor phase osmometry⁴ is 0.884 osmol/kg water,² approximately three times that of blood serum.

Iohexol is excreted primarily through the kidneys.² The ER doctor will know from a blood test result that the patient’s kidney function is adequate. The prescribing information for iohexol² suggests that most patients will eliminate 90% of the substance unchanged within 24 hours.

Iohexol

C₁₉H₂₆I₃N₃O₉
821.1 g/mol

Chemical structure of Iohexol.

IUPAC Name: 1-N,3-N-bis(2,3-dihydroxypropyl)-5-[N-(2,3-dihydroxypropyl)acetamido]-2,4,6-triiodobenzene-1,3-dicarboxamide

Questions for students

(a) What is the radiation used in CT scanning?
(b) Why are iodine atoms or barium atoms much more radiopaque to this radiation than most other atoms in living organisms?
(a) Confirm that the chemical formula and molar mass of iohexol are C₁₉H₂₆I₃N₃O₉ and 821.1 g/mol respectively.
(b) Confirm that Omnipaque 350 contains 350 mg of
iodine per mL.
(a) Identify all organic functional groups present in iohexol.
(b) Which groups are hydrophilic, and which are hydrophobic? Why is iohexol very soluble in water?
(c) Explain why the three parts of the name io-hex-ol are appropriate.