ACR Codes: 8.3
Meta-Iodobenzylguanidine (MIBG): Neuroblastoma, ganglioneuro(blasto)ma and pheochromocytoma are tumors derived from the tissues of the sympathetic nervous system. Structurally MIBG resembles norepinephrine and guanethidine (neurosecretory-depleting agent). MIBG is taken up into the storage granules of both normal and abnormal neural crest cells. The uptake is proportional to the number of neurosecretory granules within a tumor. MIBG uptake is blocked by many drugs. Catecholamine agonists (phenylephrine, pseudoephedrine), antipsychotics (phenothiazines), tricyclic antidepressants, calcium channel blockers, long acting beta blockers (labetalol), drugs that deplete catocholamine stores (reserpine, guanethidine) and cocaine are examples of drugs that interfere with MIBG uptake. Radiolabeling is done with I-123 and I-131 (I-123: half life 13.2 hrs, energy 159 KeV; I-131: half life 8.1 days, energy 364 KeV).
I-123 MIBG is used in much larger administration activities because of its much lower absorbed radiation dose per mCi compared with I-131. In addition, current gamma camera detection crystals can more efficiently detect the 159 KeV photons. Collimation is easier at lower energy and I-123 has a higher photon flux at 24 hour imaging. For these reasons MIBG studies with
I-123 is of considerably higher quality than with I-131. Normal distribution of MIBG includes salivary glands, myocardium, liver and urine. Amount in the GI tract is variable and related to excretion into the gut. A small percentage of patients show some activity in a blocked thyroid gland, normal adrenals, lung, and skeletal muscle. In normal subjects, activity should not be seen in bone, bone marrow or spleen. Utilizing SPECT MIBG can increase certainty of interpretation over planar imaging although it has not shown to increase the number of lesions detected.
Although in this particuar case, the tumor was not identified on planar images but it was visualized on SPECT imaging. Overall, primary tumor, lymph node metastasis, bone and bone marrow metastasis are detected using MIBG.
Pheochromocytoma is a rare tumor of chromaffin cells most commonly arising from the adrenal medulla. An estimated 800 cases are diagnosed yearly in the U.S. The peak incidence is in the third to fifth decades of life. Bilateral disease is present in approximately 10% of patients. Bilaterality is much more common in familial pheochromocytoma, often found in association with the familial multiple endocrine neoplasia syndromes (MEN, types IIA and IIB). In patients with MEN type II syndromes, the risk of developing a contralateral tumor following unilateral adrenalectomy is approximately 50%. Other syndromes associated with pheochromocytoma include neurofibromatosis, von Hippel-Lindau disease, cerebellar hemangioblastoma, Sturge-Weber\'s syndrome, and tuberous sclerosis. Therefore, all patients with pheochromocytomas should be screened for MEN-2 and von Hippel-Lindau disease to avert further morbidity and mortality in the patients and their families. Extra-adrenal pheochromocytoma or functional paraganglioma occurs in approximately 10% to 15% of cases and may arise from any extra-adrenal chromaffin tissue in the body associated with sympathetic ganglia.
Extra-adrenal pheochromocytoma is most often located within the abdomen and may have greater malignant potential than adrenal pheochromocytoma. Extra-adrenal tumors usually have a poorer prognosis than adrenal tumors. Due to the production and release of catecholamines, pheochromocytomas cause hypertension. However, only 0.1% to 0.5% of all hypertension patients will be found to have a pheochromocytoma. The importance of the recognition of this disease is that over 90% of patients properly diagnosed and treated are curable.
The hypertension caused by pheochromocytoma may be sustained or paroxysmal and is often severe with occasional malignant features of encephalopathy, retinopathy and proteinuria. Less commonly, severe hypertensive reactions may occur during incidental surgery, following trauma, exercise, or micturition (in the setting of bladder pheochromocytoma) when the diagnosis is unsuspected. Other clinical features of pheochromocytoma include headache, sweating, palpitation, tachycardia and severe anxiety along with epigastric or chest pain. The diagnosis of pheochromocytoma is established by the demonstration of elevated 24-hour urinary excretion of free catecholamines (norepinephrine and epinephrine) or catecholamine metabolites (VMA and total metanephrines). The measurement of plasma catecholamines can also be of value in the diagnosis of pheochromocytoma. However, the measurement of plasma catecholamines has limited sensitivity and specificity. Plasma metanephrines have been reported to be more sensitive than plasma catecholamines.
Once the diagnosis is confirmed by biochemical determinations the localization and extent of disease should be determined. Ninety-seven percent are found in the abdomen, 2% to 3% in the thorax, and 1% in the neck. The initial studies should be a chest film and abdominal computed tomographic (CT) scan.
I123meta-iodobenzylguanidine (MIBG) has been found to be useful as a scintigraphic localization agent. If the tumor is not adequately localized by these methods then magnetic resonance imaging (MRI), or rarely, vena cava catheterization with selective venous sampling for catecholamines may be indicated. CT and MRI scans are about equally sensitive (98%-100%), while MIBG scanning has a sensitivity of only 80%. However, MIBG scanning has a specificity of 100%, compared to specificity of 70% for CT and MRI. Surgical resection is the standard curative modality. If the primary tumor is localized to the adrenal gland and is benign, then survival is that of the normal age-matched population. In patients with unresectable, recurrent, or metastatic disease long-term survival is possible however, the overall 5-year survival is less than 50%. Pharmacologic treatment of the catecholamine excess is mandatory and surgery, radiation therapy, or chemotherapy may provide palliative benefit.
Reference(s): Gelfand, MJ. Meta-Iodobenzylguanidine in Children. Semin Nucl Med. 1993 Jul;23(3):231-42. Review.
Gelfand MJ, Elgazzar AH, Kriss VM, Masters PR, Golsh GJ. Iodine-123-MIBG SPECT versus planar imaging in children with neural crest tumors. J Nucl Med. 1994 Nov;35(11):1753-7.
Neumann HP, Berger DP, Sigmund G, et al.:Pheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel-Lindau disease. N Engl J Med 329 (21): 1531-8, 1993.
Wilson JD, Foster DW, Kronenberg HM, et al., eds.: Williams Textbook of Endocrinology. 9th ed. Philadelphia, Pa: W.B. Saunders Company, 1998, pp 705-716.
McEwan AJ, Shapiro B, Sisson JC, et al.: Radio-iodobenzylguanidine for the scintigraphic location and therapy of adrenergic tumors. Semin Nucl Med 15 (2): 132-53, 1985.
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