Iobenguane I-131 – Uses, Dosage, Side Effects, Interactions

Iobenguane Sulfate I-131 is the sulfate salt form of iobenguane, an iodine-131 labeled aralkylguanidine norepinephrine analog used as a diagnostic imaging tracer. Iobenguane is structurally related to guanethidine and norepinephrine. This agent, functioning as a false substrate of norepinephrine, is taken up and localized? in the granules of pre-synaptic adrenergic neurons, thus making this compound useful for the imaging of neuroendocrine tissues and tumors. Synthetic guanethidine derivative that locates phaeochromocytomas and neuroblastomas. The radioisotope used can either be iodine-123 for imaging or iodine-131 for the destruction of tissues that metabolize noradrenaline. Iodine 123 is a cyclotron-produced radionuclide that decays to Te 123 by electron capture. Images are produced by an I123 MIBG scintigraphy. FDA approved on September 19, 2008.

Mechanism of action

The structure of iobenguane is similar to noradrenaline so it can be taken up by adrenergic tissue in the adrenal medulla, liver?, heart, and spleen?. Once taken up by noradrenaline transporters in the adrenergic nerve terminals, it is stored in the presynaptic storage vesicles. The radioactive iodine component is responsible for its imaging properties.

AdreView is a diagnostic radiopharmaceutical that contains a small quantity of iobenguane that is not expected to produce a pharmacodynamic effect. Patients with renal? insufficiency may experience increased radiation exposure and impaired imaging results.

Indications

• Detection of primary and metastatic pheochromocytoma or neuroblastoma
• Pheochromocytoma, Metastatic
• Metastatic Neuroblastoma
• Primary Neuroblastomas
• Primary Pheochromocytomas
• Unresectable, locally advanced iobenguane-scan positive Paraganglioma
• Unresectable, locally advanced iobenguane-scan positive Pheochromocytomas
• Unresectable, metastatic iobenguane-scan positive Paraganglioma
• Unresectable, metastatic iobenguane-scan positive Pheochromocytomas

Use in Cancer

Iobenguane I 131 is approved to treat:

• Pheochromocytoma or paraganglioma is malignant? and requires systemic? anticancer therapy. It is used in adults and children aged 12 years or older whose iobenguane scan was positive and whose disease is locally advanced, has spread to other parts of the body, or cannot be removed by surgery.

Iobenguane I 131 is also being studied in the treatment of other types of cancer.

Contraindication?

The following conditions are contraindicated? with this drug. Check with your physician if you have any of the following:

• a condition with low thyroid? hormone levels
• anemia?
• decreased blood platelets
• low levels of a type of white blood cell called neutrophils
• high blood pressure
• pregnancy
• a patient who is producing milk and breastfeeding
• chronic kidney disease? stage 2 (mild?)
• chronic? kidney? disease stage 3A (moderate?)
• chronic kidney disease stage 3B (moderate)

Dosage?

Recommended Dosage

Administer thyroid blockade and other pre- and concomitant medications as recommended

Dosimetric Dose

The recommended AZEDRA dosimetric dose administered as an intravenous injection is:

• Patients weighing greater than 50 kg: 185 to 222 MBq (5 or 6 mCi)
• Patients weighing 50 kg or less: 3.7 MBq/kg (0.1 mCi/kg)

Dosimetry And Biodistribution Assessment?

Following the AZEDRA dosimetric dose:

• Acquire anterior/posterior whole-body gamma camera images within 1 hour of the AZEDRA dosimetric dose and prior to patient voiding (Day 0; Scan 1).
• Acquire additional images on Day 1 or 2 following patient voiding (Scan 2).
• Acquire additional images between Days 2-5 following patient voiding (Scan 3).

For each individual patient, calculate the radiation dose estimates to normal organs and tissues per unit activity [D (organ)] of administered dose using data extracted from these 3 images. Calculate in accordance with the Medical Internal Radiation Dose (MIRD) schema or related methodology. Whenever possible, use patient-specific organ masses (e.g. estimated from imaging).

Therapeutic? Dosage

The recommended AZEDRA therapeutic dose is based on body weight and reduced, if necessary, based on the dosimetry data. Administer a total of 2 therapeutic doses intravenously a minimum of 90 days apart.

Weight-Based Dose per Therapeutic Cycle

• Patients weighing greater than 62.5 kg: 18,500 MBq (500 mCi)
• Patients weighing 62.5 kg or less: 296 MBq/kg (8 mCi/kg)

Determine if Dose Reduction is Needed Based on Critical Organ Limits

• Calculate the estimated critical organ absorbed dose by multiplying the dosimetry-derived radiation absorbed dose per unit activity [D (organ)] by weight-based therapeutic total activity (Aw).
• If the resulting estimated critical organ absorbed dose is less than the threshold absorbed dose (T) shown in Table 1, no dose adjustment is necessary
• If the resulting estimated critical organ absorbed dose exceeds the threshold absorbed dose (T) shown in Table 1, calculate the reduced therapeutic total activity (i.e., the cumulative activity that would be administered in 2 therapeutic cycles) using the following equation:
• Reduced Therapeutic Total Activity= Aw x[T ÷ {Aw x D (organ)}]  Example: A 75 kg patient qualifies for a therapeutic total activity of 1000 mCi (Aw). For the kidneys?, the dosimetry yields an estimated critical organ absorbed dose per unit activity of 0.027 Gy/mCi [D (kidney)]. Thus, the estimated critical organ absorbed dose to the kidney is 27 Gy [Aw x D (organ)], which exceeds the threshold absorbed dose for the kidneys (T) of 18 Gy (Table 1). Using the equation above the reduced therapeutic total activity to be administered to this patient is 666.7 mCi. 1000 mCi x [18 Gy ÷ {1000 mCi x 0.027 mCi/Gy}]

Side Effects

The Most Common

• chest pressure, dry cough?, feeling short of breath;
• easy bruising?, unusual bleeding, purple or red spots under your skin;
• thyroid symptoms–extreme tired feeling, dry skin, joint pain? or stiffness?, muscle pain? or weakness?, hoarse voice, feeling more sensitive to cold temperatures, weight gain;
• low white blood cell counts–fever?, mouth sores, skin sores, sore throat?, cough, trouble breathing; or
• low red blood cells (anemia)–pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet.
• low blood cell counts;
• feeling tired;
• nausea, vomiting;
• dizziness; or
• low blood pressure (feeling light-headed)

Drug Interaction

Pregnancy and Lactation

Pregnancy Category C

Pregnancy

Based on its mechanism of action, AZEDRA can cause fetal harm. There are no available data on AZEDRA use in pregnant women. No animal studies using iobenguane I 131 have been conducted to evaluate its effect on female reproduction and embryo-fetal development; however, all radiopharmaceuticals, including AZEDRA, have the potential to cause fetal harm. Advise pregnant women of the risk to a fetus.

Lactation

There are no data on the presence of iobenguane I 131 in human milk or its effects on the breastfed infant or milk production. No lactation studies in animals were conducted. Because of the potential risk for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with AZEDRA and for 80 days after the final dose.

References