Iobenguane ¹²³I

Iobenguane is similar in structure to the antihypertensive drug guanethedine and to the neurotransmitter norepinephrine (NE). Iobenguane is, therefore, largely subject to the same uptake and accumulation pathways as NE. Iobenguane is taken up by the NE transporter in adrenergic nerve terminals and stored in the presynaptic storage vesicles. Iobenguane accumulates in adrenergically innervated tissues such as the adrenal medulla, salivary glands, heart, liver, spleen and lungs as well as tumors derived from the neural crest. By labeling iobenguane with the isotope iodine 123, it is possible to obtain scintigraphic images of the organs and tissues in which the radiopharmaceutical accumulates.

Iobenguane ¹²³I is a diagnostic radiopharmaceutical which contains a small quantity of iobenguane that is not expected to produce a pharmacodynamic effect. To minimize radiation dose to the thyroid gland, this organ should be blocked before dosing. Since iobenguane is excreted mainly via the kidneys, patients with severe renal insufficiency may experience increased radiation exposure and impaired imaging results. Frequent voiding should be encouraged after administration to minimize the radiation dose to the bladder.

Iobenguane is rapidly cleared from the blood and accumulates in adrenergically innervated tissues. Retention is especially prolonged in highly adrenergically innervated tissues (e.g., the adrenal medulla, heart, and salivary glands).

The majority of the iobenguane dose is excreted unaltered by the kidneys via glomerular filtration. A rapid initial clearance of circulating iobenguane is observed, followed by a slow clearance as iobenguane is released from other compartments. In patients with normal renal function, 70 to 90% of the administered dose is recovered unaltered in urine within 4 days. Iobenguane is not cleared by dialysis. Most of the remaining radioactivity recovered in the urine is in the form of the radioiodinated metabolite m-iodohippuric acid (MIHA) (typically ≤10%) and free radioiodide (typically ≤6%). The enzymatic process responsible for metabolism has not been well characterized and the pharmacologic activity of these metabolites has not been studied. Only a small amount (<1%) of the injected dose is eliminated via the feces.

Iobenguane sulfate testing in dogs revealed electrocardiographic (ECG) changes after administration of 202 times the mg/m² conversion of the maximum human dose for a 60 kg adult; the no observable effect level (NOEL) was not determined. When iobenguane was tested in a cell system stably expressing hERG-1 potassium channels, inhibition of potassium channels was not observed at an 80 μM iobenguane concentration and the IC₅₀ was 487 μM.