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

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

(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, 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 b ...

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

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 is a rare tumor of the adrenal medulla composed of chromaffin cells and is part of the paraganglioma (PGL) family of tumors, being defined as an intra-adrenal PGL. These neuroendocrine tumors can be sympathetic, where they relea ...

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 head, neck, chest, abdomen, or Vertebral column, spine. Symptoms may include ...

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 nu ...

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 adrenal medulla, medulla of the adrenal glands in mammals. These cells serve a variety of functions such as serving as a response to ...

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, an ...

. 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 Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

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 ''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 cellular processes; the co ...

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 tumour, 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 p ...

, and

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

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...

adrenal medulla The adrenal medulla () is the inner 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 cells that secrete catecho ...

salivary glands The salivary glands in many vertebrates including mammals are exocrine glands that produce saliva through a system of Duct (anatomy), ducts. Humans have three paired major salivary glands (Parotid gland, parotid, Submandibular gland, submandibula ...

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

, and

spleen The spleen (, from Ancient Greek '' σπλήν'', splḗn) is an organ (biology), organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The spleen plays important roles in reg ...

, as well as in tumors that originate in the

neural crest The neural crest is a ridge-like structure that is formed transiently between the epidermal ectoderm and neural plate during vertebrate development. Neural crest cells originate from this structure through the epithelial-mesenchymal transition, ...

. 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 13.2232 hours; the decay by electron capture to t ...

it serves as a whole-body, non-invasive

scintigraphic Nuclear medicine (nuclear radiology, nucleology), is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging is, in a sense, ''radiology done inside out'', because it reco ...

screening for germ-line,

somatic Somatic may refer to: * Somatic (biology), referring to the cells of the body in contrast to the germ line cells ** Somatic cell, a non-gametic cell in a multicellular organism * Somatic nervous system, the portion of the vertebrate nervous syst ...

, 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 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, 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, r ...

(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 eye ...

, 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 Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. They most commonly occur in the intestine, whe ...

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 The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

-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 ...

or Lugol's solution containing 100 mg iodide, weight adjusted for children and given an hour before injection. EANM guidelines, endorsed by the SNMMI, 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 five to seven 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

approved Approved may refer to: *Approved drug, a preparation that has been validated for a therapeutic use by a ruling authority of a government *''Approved'', a 2013 album by Chester Thompson Chester Thompson (born December 11, 1948) is an American dr ...

it on July 30, 2018. The drug is developed by Progenics Pharmaceuticals.

References

External links

* * {{Authority control Adrenergic receptor antagonists Diagnostic endocrinology Guanidines 3-Iodophenyl compounds Radiopharmaceuticals