Iobenguane

Iobenguane, or MIBG, is an aralkylguanidine analog of the adrenergic neurotransmitter norepinephrine and a radiopharmaceutical. It acts as a blocking agent for adrenergic neurons. When radiolabeled, it can be used in nuclear medicinal diagnostic techniques as well as in neuroendocrine antineoplastic treatments.

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 scan" redirects here. For the MIBI scan, see Technetium (99mTc) sestamibi.
Iobenguane
Clinical data
Other namesmeta-iodobenzylguanidine
mIBG, MIBG
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC8H10IN3
Molar mass275.093 g·mol−1
3D model (JSmol)
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It localizes to adrenergic tissue and thus can be used to identify the location of tumors[1] such as pheochromocytomas and neuroblastomas. With I-131 it can also be used to eradicate tumor cells that take up and metabolize norepinephrine.

Usage and mechanism

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

Imaging procedures

MIBG radiolabeled with iodine 131 or 123 concentrates in endocrine tumors, most commonly neuroblastomas, paragangliomas, and pheochromocytomas. 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. MIBG serves as a whole-body, non-invasive scintigraphic screening for germ-line, somatic, benign, and malignant neoplasms originating from the adrenal glands. It is able to 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. Large doses of the compound have been used in trials to selectively administer radiotherapy to malignant pheochromocytomas as well as neuroblastomas.

Side effects

Common side effects post imaging includes lymphopenia, neutropenia, anemia, thrombocytopenia, and fatigue. Nausea, vomiting, hypertension, and dizziness have also been observed. 6.8% of patients in a study who received therapeutic dosing of iobenguane developed acute leukemia or myelodysplastic syndrome.

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 the risk of thyroid ablation ( in the case of I-131). The minimal risk of thyroid carcinogenesis is also reduced as a result.

The FDA-approved dosing of potassium iodide for this purpose are as follows: infants less than 1 month old, 16 mg; children 1 month to 3 years, 32 mg; children 3 years to 18 years, 65 mg; adults 130 mg.[2] However, some sources recommend alternative dosing regimens.[3]

Not all sources are in agreement on the necessary duration of thyroid blockade, although agreement appears to have been reached about the necessity of blockade for both scintigraphic and therapeutic applications of iobenguane. Commercially available iobenguane is labeled with iodine-123, and product labeling recommends administration of potassium iodide 1 hour prior to administration of the radiopharmaceutical for all age groups,[4] while the European Associated of Nuclear Medicine recommends (for iobenguane labeled with either I-131 or I-123,) that potassium iodide administration begin one day prior to radiopharmaceutical administration, and continue until the day following the injection, with the exception of newborns, who do not require potassium iodide doses following radiopharmaceutical injection.[3]

Product labeling for diagnostic iodine-131 iobenguane recommends potassium iodide administration one day before injection and continuing 5 to 7 days following.[5] Iodine-131 iobenguane used for therapeutic purposes requires a different pre-medication duration, beginning 24–48 hours prior to iobenguane injection and continuing 10–15 days following injection.[6]

Alternative imaging modality for pheochromocytoma

The FDOPA PET/CT scan has proven to be nearly 100% sensitive for detection of pheochromocytomas, vs. 90% for MIBG scans.[7][8][9] Centers which offer FDOPA PET/CT, however, are rare.

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.[10][11]

References
  1. Scarsbrook AF, Ganeshan A, Statham J, et al. (2007). "Anatomic and functional imaging of metastatic carcinoid tumors". Radiographics. 27 (2): 455–77. doi:10.1148/rg.272065058. PMID 17374863.
  2. Kowalsky RJ, Falen, SW. Radiopharmaceuticals in Nuclear Pharmacy and Nuclear Medicine. 2nd ed. Washington DC: American Pharmacists Association; 2004.
  3. (PDF) https://web.archive.org/web/20060602173455/http://www.eanm.org/scientific_info/guidelines/gl_paed_mibg.pdf. Archived from the original (PDF) on 2006-06-02. Retrieved 2011-10-07. Missing or empty |title= (help)
  4. "Archived copy" (PDF). Archived from the original (PDF) on 2011-08-23. Retrieved 2010-07-30.CS1 maint: archived copy as title (link)
  5. Iobenguane Sulfate I 131 Injection Diagnostic package insert. Bedford, MA: CIS-US, Inc. July 1999.
  6. "Archived copy" (PDF). Archived from the original (PDF) on 2011-10-07. Retrieved 2011-10-07.CS1 maint: archived copy as title (link)
  7. 6-[18FFluorodopamine Positron Emission Tomographic (PET) Scanning for Diagnostic Localization of Pheochromocytoma. Pacek et al. 2001] full text
  8. Pheochromocytoma Imaging Updated May 2017
  9. Luster M, Karges W, Zeich K, Pauls S, Verburg FA, Dralle H, et al. (2010). "Clinical value of (18)F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography ((18)F-DOPA PET/CT) for detecting pheochromocytoma". European Journal of Nuclear Medicine and Molecular Imaging. 37 (3): 484–93. doi:10.1007/s00259-009-1294-7. PMID 19862519.
  10. AZEDRA® (iobenguane I 131) Jul 2018
  11. FDA approves first treatment for rare adrenal tumors Jul 2018
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