Iobenguane, or MIBG, is an aralkylguanidine analog of the adrenergic neurotransmitter

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...

(noradrenaline), typically used as a

radiopharmaceutical Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which ...

. It acts as a blocking agent for adrenergic neurons. When

radiolabeled A radioactive tracer, radiotracer, or radioactive label is a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactive decay it can be used to explore the mechanism of chemical reactions by tr ...

, it can be used in nuclear medicinal diagnostic and therapy techniques as well as in

neuroendocrine Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules (hormones) into the blood. In this way they bri ...

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemother ...

treatments. It localizes to adrenergic tissue and thus can be used to identify the location of

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s such as

pheochromocytoma Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred t ...

s and

neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in ...

s. With

iodine-131 Iodine-131 (131I, I-131) is an important radioisotope of iodine discovered by Glenn Seaborg and John Livingood in 1938 at the University of California, Berkeley. It has a radioactive decay half-life of about eight days. It is associated with n ...

it can also be used to treat tumor cells that take up and metabolize norepinephrine.

Usage and mechanism

MIBG is absorbed by and accumulated in granules of adrenal medullary

chromaffin cell Chromaffin cells, also called pheochromocytes (or phaeochromocytes), are neuroendocrine cells found mostly in the medulla of the adrenal glands in mammals. These cells serve a variety of functions such as serving as a response to stress, monito ...

s, as well as in pre-synaptic adrenergic neuron granules. The process in which this occurs is closely related to the mechanism employed by norepinephrine and its transporter

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and p ...

. The

norepinephrine transporter The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene. NET is a monoamine transporter and is responsible for the sodium- ...

(NET) functions to provide norepinephrine uptake at the synaptic terminals and adrenal chromaffin cells. MIBG, by bonding to NET, finds its roles in imaging and therapy.

Metabolites and excretion

Less than 10% of the administered MIBG gets

metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

into m-iodohippuric acid (MIHA), and the mechanism for how this metabolite is produced is unknown.

Diagnostic imaging

MIBG concentrates in endocrine tumors, most commonly neuroblastoma,

paraganglioma A paraganglioma is a rare neuroendocrine neoplasm that may develop at various body sites (including the head, neck, thorax and abdomen). When the same type of tumor is found in the adrenal gland, they are referred to as a pheochromocytoma. They a ...

, and

. It also accumulates in norepinephrine transporters in adrenergic nerves in the

heart The heart is a muscular Organ (biology), organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as ca ...

lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of ...

adrenal medulla The adrenal medulla ( la, medulla glandulae suprarenalis) is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of chromaffin cell ...

salivary glands The salivary glands in mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands ( parotid, submandibular, and sublingual), as well as hundreds of minor salivary glands. Salivary gl ...

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...

, and

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

, as well as in tumors that originate in the

neural crest Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, per ...

. When labelled with

iodine-123 Iodine-123 (123I) is a radioactive isotope of iodine used in nuclear medicine imaging, including single-photon emission computed tomography (SPECT) or SPECT/CT exams. The isotope's half-life is 13.2230 hours; the decay by electron capture to tellu ...

it serves as a whole-body, non-invasive

scintigraphic Nuclear medicine or nucleology is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging, in a sense, is "radiology done inside out" because it records radiation emitting ...

screening for

germ-line In biology and genetics, the germline is the population of a multicellular organism's cells that pass on their genetic material to the progeny ( offspring). In other words, they are the cells that form the egg, sperm and the fertilised egg. Th ...

, somatic, benign, and malignant

neoplasm A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s originating in the adrenal glands. It can detect both intra and extra-adrenal disease. The imaging is highly sensitive and specific. Iobenguane concentrates in presynaptic terminals of the heart and other autonomically innervated organs. This enables the possible

non-invasive A medical procedure is defined as ''non-invasive'' when no break in the skin is created and there is no contact with the mucosa, or skin break, or internal body cavity beyond a natural or artificial body orifice. For example, deep palpation and p ...

use as an in vivo probe to study these systems. Alternatives to imaging with ¹²³I-MIBG, for certain indications and under clinical and research use, include the positron-emitting isotope

iodine-124 There are 37 known isotopes of iodine (53I) from 108I to 144I; all undergo radioactive decay except 127I, which is stable. Iodine is thus a monoisotopic element. Its longest-lived radioactive isotope, 129I, has a half-life of 15.7 million year ...

, and other radiopharmaceuticals such as ⁶⁸Ga-DOTA and ¹⁸F-FDOPA for

positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...

(PET). ¹²³I-MIBG imaging on a

gamma camera A gamma camera (γ-camera), also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy. The applications of scintigraphy include early drug development ...

can offer significantly higher cost-effectiveness and availability compared to PET imaging, and is particularly effective where ¹³¹I-MIBG therapy is subsequently planned, due to their directly comparable uptake.

Side effects

Side effects post imaging are rare but can include

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

pallor Pallor is a pale color of the skin that can be caused by illness, emotional shock or stress, stimulant use, or anemia, and is the result of a reduced amount of oxyhaemoglobin and may also be visible as pallor of the conjunctivae of the eyes o ...

, vomiting, and abdominal pain.

Radionuclide therapy

MIBG can be radiolabelled with the beta emitting radionuclide ¹³¹I for the treatment of certain pheochromocytomas, paragangliomas,

carcinoid tumor A carcinoid (also carcinoid tumor) is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut (jejunum, ileum, appendix, and cecum) a ...

s, neuroblastomas, and

medullary thyroid cancer Medullary thyroid cancer is a form of thyroid carcinoma which originates from the parafollicular cells (C cells), which produce the hormone calcitonin.Hu MI, Vassilopoulou-Sellin R, Lustig R, Lamont JP"Thyroid and Parathyroid Cancers"in Pazdur R, ...

Thyroid precautions

Thyroid blockade with (nonradioactive) potassium iodide is indicated for nuclear medicine scintigraphy with iobenguane/mIBG. This competitively inhibits radioiodine uptake, preventing excessive radioiodine levels in the thyroid and minimizing risk of thyroid ablation (in treatment with ¹³¹I). The minimal risk of thyroid cancer is also reduced as a result. The dosing regime for the FDA-approved commercial ¹²³I-MIBG product Adreview is

potassium iodide Potassium iodide is a chemical compound, medication, and dietary supplement. It is a medication used for treating hyperthyroidism, in radiation emergencies, and for protecting the thyroid gland when certain types of radiopharmaceuticals are u ...

Lugol's solution Lugol's iodine, also known as aqueous iodine and strong iodine solution, is a solution of potassium iodide with iodine in water. It is a medication and disinfectant used for a number of purposes. Taken by mouth it is used to treat thyrotoxicosi ...

containing 100 mg iodide, weight adjusted for children and given an hour before injection. EANM guidelines, endorsed by the

SNMMI The Society of Nuclear Medicine and Molecular Imaging (SNMMI), formerly the Society of Nuclear Medicine, is a nonprofit scientific and professional organization that promotes the science, technology and practical application of nuclear medicine a ...

, suggest a variety of regimes in clinical use, for both children and adults. Product labeling for diagnostic ¹³¹I iobenguane recommends giving potassium iodide one day before injection and continuing 5 to 7 days following. ¹³¹I iobenguane used for therapeutic purposes requires a different pre-medication duration, beginning 24–48 hours before iobenguane injection and continuing 10–15 days after injection.

Clinical trials

Iobenguane I 131 for cancers

Iobenguane I 131, marketed under the trade name Azedra, has had a clinical trial as a treatment for malignant, recurrent or unresectable pheochromocytoma and paraganglioma, and the FDA approved it on July 30, 2018. The drug is developed by Progenics Pharmaceuticals.

References

External links

* * * * * {{Authority control Iodoarenes Radiopharmaceuticals Guanidines Adrenergic receptor antagonists