Iobenguane

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Iobenguane
Iobenguane.svg
Clinical data
Trade names Adreview, Azedra
Other namesmeta-iodobenzylguanidine
mIBG, MIBG
License data
Routes of
administration
Intravenous
ATC code
Legal status
Legal status
Identifiers
  • 1-(3-iodobenzyl)guanidine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C8H10IN3
Molar mass 275.093 g·mol−1
3D model (JSmol)
  • C1=CC(=CC(=C1)I)CNC(=N)N
  • InChI=1S/C8H10IN3/c9-7-3-1-2-6(4-7)5-12-8(10)11/h1-4H,5H2,(H4,10,11,12) X mark.svgN
  • Key:PDWUPXJEEYOOTR-UHFFFAOYSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Iobenguane, or MIBG, is an aralkylguanidine analog of the adrenergic neurotransmitter norepinephrine (noradrenaline), typically used as a radiopharmaceutical. [3] 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 chemotherapy treatments.

Contents

It localizes to adrenergic tissue and thus can be used to identify the location of tumors such as pheochromocytomas and neuroblastomas. [4] With iodine-131 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 cells, 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. [5] [6] The norepinephrine transporter (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 into m-iodohippuric acid (MIHA), and the mechanism for how this metabolite is produced is unknown. [7]

Diagnostic imaging

Pheochromocytoma seen as dark sphere in center of the body (it is in the left adrenal gland). Image is by MIBG scintigraphy, with radiation from radioiodine in the MIBG. Two images are seen of the same patient from front and back. Note dark image of the thyroid due to unwanted uptake of iodide radioiodine from breakdown of the pharmaceutical, by the thyroid gland in the neck. Uptake at the side of the head are from the salivary glands. Radioactivity is also seen in the bladder, from normal renal excretion of iodide. Pheochromocytoma Scan.jpg
Pheochromocytoma seen as dark sphere in center of the body (it is in the left adrenal gland). Image is by MIBG scintigraphy, with radiation from radioiodine in the MIBG. Two images are seen of the same patient from front and back. Note dark image of the thyroid due to unwanted uptake of iodide radioiodine from breakdown of the pharmaceutical, by the thyroid gland in the neck. Uptake at the side of the head are from the salivary glands. Radioactivity is also seen in the bladder, from normal renal excretion of iodide.

MIBG concentrates in endocrine tumors, most commonly neuroblastoma, paraganglioma, and pheochromocytoma. It also accumulates in norepinephrine transporters in adrenergic nerves in the heart, lungs, adrenal medulla, salivary glands, liver, and spleen, as well as in tumors that originate in the neural crest. When labelled with iodine-123 it serves as a whole-body, non-invasive scintigraphic screening for germ-line, somatic, benign, and malignant neoplasms originating in the adrenal glands. It can detect both intra and extra-adrenal disease. The imaging is highly sensitive and specific. [8] [9]

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. [10] [11]

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 (PET). [9] [12] [13] 123I-MIBG imaging on a gamma camera 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. [14] [9] [15]

Side effects

Side effects post imaging are rare but can include tachycardia, pallor, vomiting, and abdominal pain. [9]

Radionuclide therapy

MIBG can be radiolabelled with the beta emitting radionuclide 131I for the treatment of certain pheochromocytomas, paragangliomas, carcinoid tumors, neuroblastomas, and medullary thyroid cancer. [16]

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. [9] [17]

The dosing regime for the FDA-approved commercial 123I-MIBG product Adreview is potassium iodide or Lugol's solution containing 100 mg iodide, weight adjusted for children and given an hour before injection. [18] EANM guidelines, endorsed by the SNMMI, suggest a variety of regimes in clinical use, for both children and adults. [9] [12]

Product labeling for diagnostic 131I iobenguane recommends giving potassium iodide one day before injection and continuing 5 to 7 days following. [19] 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. [16]

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. [20] [21]

Related Research Articles

<span class="mw-page-title-main">Catecholamine</span> Class of chemical compounds

A catecholamine is a monoamine neurotransmitter, an organic compound that has a catechol and a side-chain amine.

Radionuclide therapy uses radioactive substances called radiopharmaceuticals to treat medical conditions, particularly cancer. These are introduced into the body by various means and localise to specific locations, organs or tissues depending on their properties and administration routes. This includes anything from a simple compound such as sodium iodide that locates to the thyroid via trapping the iodide ion, to complex biopharmaceuticals such as recombinant antibodies which are attached to radionuclides and seek out specific antigens on cell surfaces.

<span class="mw-page-title-main">Pheochromocytoma</span> Type of neuroendocrine tumor

Pheochromocytoma 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 to as a paraganglioma. These neuroendocrine tumors typically release massive amounts of catecholamines which result in the most common symptoms, including hypertension, tachycardia, and sweating. Rarely, some tumors may secrete little to no catecholamines, making diagnosis difficult. While tumors of the head and neck are parasympathetic, their sympathetic counterparts are predominantly located in the abdomen and pelvis, particularly concentrated at the organ of Zuckerkandl.

<span class="mw-page-title-main">Adrenal medulla</span> Central part of the adrenal gland

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 catecholamines, including epinephrine (adrenaline), norepinephrine (noradrenaline), and a small amount of dopamine, in response to stimulation by sympathetic preganglionic neurons.

<span class="mw-page-title-main">Chromaffin cell</span> Neuroendocrine cells found in adrenal medulla in mammals

Chromaffin cells, also called pheochromocytes, 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, monitoring carbon dioxide and oxygen concentrations in the body, maintenance of respiration and the regulation of blood pressure. They are in close proximity to pre-synaptic sympathetic ganglia of the sympathetic nervous system, with which they communicate, and structurally they are similar to post-synaptic sympathetic neurons. In order to activate chromaffin cells, the splanchnic nerve of the sympathetic nervous system releases acetylcholine, which then binds to nicotinic acetylcholine receptors on the adrenal medulla. This causes the release of catecholamines. The chromaffin cells release catecholamines: ~80% of adrenaline (epinephrine) and ~20% of noradrenaline (norepinephrine) into systemic circulation for systemic effects on multiple organs, and can also send paracrine signals. Hence they are called neuroendocrine cells.

<span class="mw-page-title-main">Scintigraphy</span> Diagnostic imaging test in nuclear medicine

Scintigraphy, also known as a gamma scan, is a diagnostic test in nuclear medicine, where radioisotopes attached to drugs that travel to a specific organ or tissue (radiopharmaceuticals) are taken internally and the emitted gamma radiation is captured by gamma cameras, which are external detectors that form two-dimensional images in a process similar to the capture of x-ray images. In contrast, SPECT and positron emission tomography (PET) form 3-dimensional images and are therefore classified as separate techniques from scintigraphy, although they also use gamma cameras to detect internal radiation. Scintigraphy is unlike a diagnostic X-ray where external radiation is passed through the body to form an image.

<span class="mw-page-title-main">Potassium iodide</span> Ionic compound (KI)

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 used. In the third world it is also used for treating skin sporotrichosis and phycomycosis. It is a supplement used by people with low dietary intake of iodine. It is administered orally.

<span class="mw-page-title-main">Paraganglioma</span> Rare neuroendocrine tumour

A paraganglioma is a rare neuroendocrine neoplasm that may develop at various body sites. When the same type of tumor is found in the adrenal gland, they are referred to as a pheochromocytoma. They are rare tumors, with an overall estimated incidence of 1 in 300,000. There is no test that determines benign from malignant tumors; long-term follow-up is therefore recommended for all individuals with paraganglioma.

<span class="mw-page-title-main">Iodine-131</span> Isotope of iodine

Iodine-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 nuclear energy, medical diagnostic and treatment procedures, and natural gas production. It also plays a major role as a radioactive isotope present in nuclear fission products, and was a significant contributor to the health hazards from open-air atomic bomb testing in the 1950s, and from the Chernobyl disaster, as well as being a large fraction of the contamination hazard in the first weeks in the Fukushima nuclear crisis. This is because 131I is a major fission product of uranium and plutonium, comprising nearly 3% of the total products of fission. See fission product yield for a comparison with other radioactive fission products. 131I is also a major fission product of uranium-233, produced from thorium.

<span class="mw-page-title-main">Isotopes of iodine</span> Nuclides with atomic number of 53 but with different mass numbers

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.

<span class="mw-page-title-main">Organ of Zuckerkandl</span>

The organ of Zuckerkandl is a chromaffin body derived from the neural crest located at the bifurcation of the aorta or at the origin of the inferior mesenteric artery. It can be the source of a paraganglioma.

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 tellurium-123 emits gamma radiation with a predominant energy of 159 keV. In medical applications, the radiation is detected by a gamma camera. The isotope is typically applied as iodide-123, the anionic form.

<span class="mw-page-title-main">Vanillylmandelic acid</span> Chemical compound

Vanillylmandelic acid (VMA) is a chemical intermediate in the synthesis of artificial vanilla flavorings and is an end-stage metabolite of the catecholamines. It is produced via intermediary metabolites.

<span class="mw-page-title-main">Paraganglion</span>

A paraganglion is a group of non-neuronal cells derived of the neural crest. They are named for being generally in close proximity to sympathetic ganglia. They are essentially of two types: (1) chromaffin or sympathetic paraganglia made of chromaffin cells and (2) nonchromaffin or parasympathetic paraganglia made of glomus cells. They are neuroendocrine cells, the former with primary endocrine functions and the latter with primary chemoreceptor functions.

<span class="mw-page-title-main">Adrenal tumor</span> Medical condition

An adrenal tumor or adrenal mass is any benign or malignant neoplasms of the adrenal gland, several of which are notable for their tendency to overproduce endocrine hormones. Adrenal cancer is the presence of malignant adrenal tumors, and includes neuroblastoma, adrenocortical carcinoma and some adrenal pheochromocytomas. Most adrenal pheochromocytomas and all adrenocortical adenomas are benign tumors, which do not metastasize or invade nearby tissues, but may cause significant health problems by unbalancing hormones.

Ioflupane (<sup>123</sup>I) Chemical compound

Ioflupane (123I) is the international nonproprietary name (INN) of a cocaine analogue which is a neuro-imaging radiopharmaceutical drug, used in nuclear medicine for the diagnosis of Parkinson's disease and the differential diagnosis of Parkinson's disease over other disorders presenting similar symptoms. During the DaT scan procedure it is injected into a patient and viewed with a gamma camera in order to acquire SPECT images of the brain with particular respect to the striatum, a subcortical region of the basal ganglia. The drug is sold under the brand name Datscan and is manufactured by GE Healthcare, formerly Amersham plc.

Nuclear medicine physicians, also called nuclear radiologists or simply nucleologists, are medical specialists that use tracers, usually radiopharmaceuticals, for diagnosis and therapy. Nuclear medicine procedures are the major clinical applications of molecular imaging and molecular therapy. In the United States, nuclear medicine physicians are certified by the American Board of Nuclear Medicine and the American Osteopathic Board of Nuclear Medicine.

<span class="mw-page-title-main">Iodocholesterol</span> Chemical compound

Iodocholesterol, or 19-iodocholesterol, also as iodocholesterol (131I) (INN) and NP-59, is a derivative of cholesterol with an iodine atom in the C19 position and a radiopharmaceutical. When the iodine atom is a radioactive isotope, it is used as an adrenal cortex radiotracer in the diagnosis of patients suspected of having Cushing's syndrome, hyperaldosteronism, pheochromocytoma, and adrenal remnants following total adrenalectomy.

<span class="mw-page-title-main">Radioactive iodine uptake test</span>

The radioactive iodine uptake test is a type of scan used in the diagnosis of thyroid problems, particularly hyperthyroidism. It is entirely different from radioactive iodine therapy, which uses much higher doses to destroy cancerous cells. The RAIU test is also used as a follow-up to RAI therapy to verify that no thyroid cells survived, which could still be cancerous.

<span class="mw-page-title-main">DOTA-TATE</span> Eight amino-acid long peptide covalently bonded to a DOTA chelator

DOTA-TATE is an eight amino acid long peptide, with a covalently bonded DOTA bifunctional chelator.

References

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  2. "Azedra- iobenguane i-131 injection, solution". DailyMed. 8 April 2021. Retrieved 21 May 2022.
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  6. Davidoff AM (2010). "Neuroblastoma". In Holcomb GW, Murphy JP, Ostlie DJ (eds.). Ashcraft's pediatric surgery (5th ed.). Philadelphia: Saunders/Elsevier. pp. 872–894. doi:10.1016/B978-1-4160-6127-4.00068-9. ISBN   978-1-4160-6127-4. Metaiodobenzylguanidine (MIBG) is transported to and stored in the distal storage granules of chromaffin cells in the same way as norepinephrine.
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