|Patent ID||Title||Submitted Date||Granted Date|
|US7658910||PREPARATION OF RADIOLABELLED HALOAROMATICS VIA POLYMER-BOUND INTERMEDIATES||
|US2008241063||Combination set of Meta-Iodobenzyl guanidine freezing crystal and making method thereof and method for making a radioactive iodine marker||
|US7273601||Preparation of radiolabelled haloaromatics via polymer-bound intermediates||
|US6461585||Preparation of radiolabelled haloaromatics via polymer-bound intermediates||
|US2010274052||PREPARATION OF RADIOLABELLED HALOAROMATICS VIA POLYMER-BOUND INTERMEDIATES||
Home » Posts tagged '131I-MIBG'
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Iobenguane I 131
July 30, 2018
The U.S. Food and Drug Administration today approved Azedra (iobenguane I 131) injection for intravenous use for the treatment of adults and adolescents age 12 and older with rare tumors of the adrenal gland (pheochromocytoma or paraganglioma) that cannot be surgically removed (unresectable), have spread beyond the original tumor site and require systemic anticancer therapy. This is the first FDA-approved drug for this use.
“Many patients with these ultra-rare cancers can be treated with surgery or local therapies, but there are no effective systemic treatments for patients who experience tumor-related symptoms such as high blood pressure,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Patients will now have an approved therapy that has been shown to decrease the need for blood pressure medication and reduce tumor size in some patients.”
Pheochromocytomas are rare tumors of the adrenal glands. These glands are located right above the kidneys and make hormones including stress hormones called epinephrines and norepinephrines. Pheochromocytomas increase the production of these hormones, leading to hypertension (high blood pressure) and symptoms such as headaches, irritability, sweating, rapid heart rate, nausea, vomiting, weight loss, weakness, chest pain or anxiety. When this type of tumor occurs outside the adrenal gland, it is called a paraganglioma.
The efficacy of Azedra was shown in a single-arm, open-label, clinical trial in 68 patients that measured the number of patients who experienced a 50 percent or greater reduction of all antihypertensive medications lasting for at least six months. This endpoint was supported by the secondary endpoint, overall tumor response measured by traditional imaging criteria. The study met the primary endpoint, with 17 (25 percent) of the 68 evaluable patients experiencing a 50 percent or greater reduction of all antihypertensive medication for at least six months. Overall tumor response was achieved in 15 (22 percent) of the patients studied.
The most common severe side effects reported by patients receiving Azedra in clinical trials included low levels of white blood cells (lymphopenia), abnormally low count of a type of white blood cells (neutropenia), low blood platelet count (thrombocytopenia), fatigue, anemia, increased international normalized ratio (a laboratory test which measures blood clotting), nausea, dizziness, hypertension and vomiting.
As it is a radioactive therapeutic agent, Azedra includes a warning about radiation exposure to patients and family members, which should be minimized while the patient is receiving Azedra. The risk of radiation exposure is greater in pediatric patients. Other warnings and precautions include a risk of lower levels of blood cells (myelosuppression), underactive thyroid, elevations in blood pressure, renal failure or kidney injury and inflammation of lung tissue (pneumonitis). Myelodysplastic syndrome and acute leukemias, which are cancers of the blood and bone marrow, were observed in patients who received Azedra, and the magnitude of this risk will continue to be studied. Azedra can cause harm to a developing fetus; women should be advised of the potential risk to the fetus and to use effective contraception after receiving Azedra. Radiation exposure associated with Azedra may cause infertility in males and females.
The FDA granted this application Fast Track, Breakthrough Therapy and Priority Review designations. Azedra also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.
The FDA granted the approval of Azedra to Progenics Pharmaceuticals, Inc.
Iobenguane (131I); Iobenguane I 131; Iobeguane I 131; 3-Iodobenzylguanidine; 131I-MIBG; Azedra
77679-27-7 CAS NUMBER
PATENT US 4584187
- Iobenguane (131I)
- Iobenguane I 131
- Ultratrace Iobenguane 131I
|Molecular Weight:||279.095 g/mol|
|Molecular Weight:||648.259 g/mol|
(iobenguane I 123) Injection for Intravenous Use
AdreView (iobenguane I 123 Injection) is a sterile, pyrogen-free radiopharmaceutical for intravenous injection. Each mL contains 0.08 mg iobenguane sulfate, 74 MBq (2 mCi) of I 123 (as iobenguane sulfate I 123) at calibration date and time on the label, 23 mg sodium dihydrogen phosphate dihydrate, 2.8 mg disodium hydrogen phosphate dihydrate and 10.3 mg (1% v/v) benzyl alcohol with a pH of 5.0 – 6.5. Iobenguane sulfate I 123 is also known as I 123 meta-iodobenzlyguanidine sulfate and has the following structural formula:
Iodine 123 is a cyclotron-produced radionuclide that decays to Te 123 by electron capture and has a physical half-life of 13.2 hours.
Iobenguane I-131 is a guanidine analog with specific affinity for tissues of the sympathetic nervous system and related tumors. The radiolabeled forms are used as antineoplastic agents and radioactive imaging agents. (Merck Index, 12th ed) MIBG serves as a neuron-blocking agent which has a strong affinity for, and retention in, the adrenal medulla and also inhibits ADP-ribosyltransferase.
Iobenguane i-131 is a Radioactive Diagnostic Agent. The mechanism of action of iobenguane i-131 is as a Radiopharmaceutical Activity.
Iobenguane I-131 is an I 131 radioiodinated synthetic analogue of the neurotransmitter norepinephrine. Iobenguane localizes to adrenergic tissue and, in radioiodinated forms, may be used to image or eradicate tumor cells that take up and metabolize norepinephrine.
Iobenguane, also known as metaiodobenzylguanidine or mIBG, or MIBG (tradename Adreview) is a radiopharmaceutical, used in a scintigraphy method called MIBG scan. Iobenguane is a radiolabeled molecule similar to noradrenaline.
The radioisotope of iodine used for the label can be iodine-123 (for imaging purposes only) or iodine-131 (which must be used when tissue destruction is desired, but is sometimes used for imaging also).
It localizes to adrenergic tissue and thus can be used to identify the location of tumors such as pheochromocytomas and neuroblastomas. With I-131 it can also be used to eradicate tumor cells that take up and metabolize norepinephrine.
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. However, some sources recommend alternative dosing regimens.
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, 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.
Product labeling for diagnostic iodine-131 iobenguane recommends potassium iodide administration one day before injection and continuing 5 to 7 days following. 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.
Alternative imaging modality for pheochromocytoma
Iobenguane I 131 for cancers
|Chemical and physical data|
|Molar mass||275.09 g/mol|
|3D model (JSmol)|
- “Iobenguane I 131 Sulfate (Intravenous Route) – MayoClinic.com”. Retrieved 2007-12-15.
- 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.
- Kowalsky RJ, Falen, SW. Radiopharmaceuticals in Nuclear Pharmacy and Nuclear Medicine. 2nd ed. Washington DC: American Pharmacists Association; 2004.
- “Archived copy” (PDF). Archived from the original (PDF) on 2011-10-07. Retrieved 2011-10-07.
- Iobenguane Sulfate I 131 Injection Diagnostic package insert. Bedford, MA: CIS-US, Inc. July 1999.
- “Archived copy” (PDF). Archived from the original (PDF) on 2011-10-07. Retrieved 2011-10-07.
- 6-[18FFluorodopamine Positron Emission Tomographic (PET) Scanning for Diagnostic Localization of Pheochromocytoma. Pacek et al. 2001] full text
- Pheochromocytoma Imaging Updated May 2017
- 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.
- FDA grants priority review to Azedra for rare neuroendocrine tumors Jan 2018
- Iodine 131-metaiodobenzylguanidine at the NCI Drug Dictionary