NEUROENDOCRINE TUMOR SCINTIGRAPHY

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1 NEUROENDOCRINE TUMOR SCINTIGRAPHY OBJECTIVES Upon completion of this course, participants will be able to do the following: Explain the mechanism of localization and biologic properties of metaiodobenzylguanidine (mibg). Explain the importance of a patient s drug history. Provide details of patient preparation for imaging with 123 I-mIBG including contraindications, warnings, and precautions. Discuss the imaging protocol for radioiodinated mibg. Recognize the clinical applications of radiolabeled mibg. INTRODUCTION Neuroendocrine tumors consist of a variety of lesions that are thought to have their origin from the embryologic neural crest cells. Depending on the type of histology, these tumors can be found in the body in numerous locations. These types of tumors may maintain the neuroendocrine appearance and secrete biologically active substances. When there is inappropriate secretion of these bioactive substances, clinical symptoms can present. 1 Paragangliomas, pheochromocytomas, and neuroblastomas are in this category of functional adrenergic tumors. Paragangliomas originating in the adrenal medulla are known as pheochromocytomas. Several significant familial syndromes, such as multiple endocrine neoplasia (MEN) type IIA and MEN type IIB, von Hipple-Lindau disease, and neurofibromatosis are linked with paragangliomas. MEN type IIA includes medullary carcinoma of the thyroid, pheochromocytoma, and hyperparathyroidism while MEN type IIB includes medullary carcinoma of the thyroid, pheochromocytoma, and ganglioneuromas. 2 The majority of pheochromocytomas are found in the adrenal medulla. Due to the intermittent, systemic release of catecholamines by this type of tumor, patients typically present with labile, severe hypertension. Headaches, sweating, anxiety, and tachycardia are also symptoms; it is thought that 10% are malignant. Bilateral disease is present in 10% of the patients. 1 Neuroblastoma is a malignant tumor that occurs in young children. The majority of these tumors (70%) arise in the retroperitoneal region while 20% originate in the chest. Catecholamines are produced in greater than 90% of neuroblastomas. 2 The two neuroendocrine tumors that will primarily be emphasized in this lesson are pheochromocytoma and neuroblastoma although others will be briefly presented Omnipath, Inc. All rights reserved. 1

2 RADIOPHARMACEUTICALS The function of the adrenal medulla in the synthesis and storage of catecholamines was instrumental in the drug development of adrenal medullary imaging radiopharmaceuticals. Due to the significant antiadrenergic activity of benzylguanidines, radioiodinated versions of these compounds were successfully studied at the University of Michigan. It was found that the meta-iodinated isomer (meta-iodobenzylguandine or mibg) was better for scintigraphy since this isomer was resistant to in vivo deiodination and because of its lower liver concentration compared to the other isomers that were investigated. 3 mibg is an analog of guanethidine. 4 Diagnostic nuclear medicine scintigraphy for neuroendocrine tumors can be conducted with radioiodinated meta-iodobenzylguanidine (mibg or iobenguane), 111 In-pentetreotide (trade name OctreoScan, Covidien), and fludeoxyglucose F-18 ( 18 F-FDG); however, this lesson will focus on 123 I-mIBG in the imaging of neuroendocrine tumors. Initially, FDA approved 131 I- iobenguane, and subsequently approved 123 I-iobenguane on September 19, The FDA approval of 123 I-iobenguane (trade name AdreView TM, GE Healthcare) is for the detection of primary and metastatic pheochromocytoma or neuroblastoma as an adjunct to other diagnostic tests. The use of 131 I-iobenguane declined significantly after 123 I-iobenguane became commercially available, and Pharmalucence discontinued production of this product for commercial distribution in Even though iobenguane is the generic name for this agent, we will use the abbreviated chemical name (mibg) for this product in most situations throughout the lesson. MECHANISM OF UPTAKE AND BIOLOGIC PROPERTIES It has been demonstrated that mibg undergoes specific uptake and storage via the adrenal medulla, the sympathetic autonomic nervous system, and tumors originating from these tissues. 5 Experiments have pointed out that radiolabeled mibg undergoes uptake into sympathetic neuroeffector cells comparable to norepinephrine via a specific catecholamine type I active uptake mechanism and that it is localized in adrenergic storage vesicles. However, unlike norepinephrine, mibg does not interact with postsynaptic α- and β- adrenergic receptors. 3 Uptake of mibg by tumors is proportional to the number of the tumor s neurosecretory (catecholamine) storage granules Omnipath, Inc. All rights reserved. 2

3 Besides being taken up in the adrenal medulla and other adrenergic and neuroblastic tumor tissues, the radiopharmaceutical is taken up in other organs having rich adrenergic innervation, such as the heart, salivary glands, and nasopharynx. 2,3 Liver, spleen, and urinary bladder (issues involved in the metabolism and excretion of mibg) are also seen during scintigraphy. 3 Because the adrenal gland s depth in the body and small size, the normal adrenal medulla is visualized faintly in 10% of patients receiving typical doses of 131 I-mIBG; however, it is seen more frequently when using 123 I-mIBG. 2 Radioiodinated mibg is demonstrated faintly in the thyroid gland. It undergoes metabolism slowly, and it has been reported that 75% to 90% of the injected radiopharmaceutical undergoes renal excretion in the unaltered state. Thus, kidney and bladder activity are also visualized. In some patients there may be neck muscle activity, bowel activity, and diffuse lung activity. 4 DRUG INTERFERENCE There are several drugs that interfere with the mechanism of uptake or storage of mibg with the result being a reduction in the uptake of mibg into the tumor cells or an increase in its egress out of the cells. This means that the sensitivity of mibg scintigraphy for the detection of tumor deposits is diminished. 1 Drugs known to interfere with mibg uptake or the storage can be classified according to the length of time they should be withheld prior to the administration of mibg. Refer to Tables 1,2, and 3 for a list of drugs that are known or expected to interfere with the sensitivity of mibg scintigraphy along with the recommended time period to withhold the interfering drugs prior to mibg administration in order to minimize false-negative results Omnipath, Inc. All rights reserved. 3

4 Table 1: Drugs That Interfere with the Sensitivity of mibg Scintigraphy 3,6 Recommended Withdrawal Time Period: 6 Weeks Desipramine Amitriptyline Amoxapine Tricyclic Antidepressants: Doxepin Imipramine Pamole Maprotiline Nortriptyline Protriptyline Trimipramine Trazadone Table 2: Drug That Interferes with the Sensitivity of mibg Scintigraphy 6 Recommended Withdrawal Time Period: 3 Weeks Labetalol 2013 Omnipath, Inc. All rights reserved. 4

5 Table 3: Drugs That Interfere with the Sensitivity of mibg Scintigraphy 3 Recommended Withdrawal Time Period: 2 Weeks Acetophenazine Chlorpromazine Chlorprothixene Droperidol Fluphenazine Tranquilizers: Haloperidol Mesoridazine Perphenazine Pimozide Prochlorperzine Promazine Triflupromazine Thioridazine Thiothixene Trifluoperazine Amphetamine Benzphetamine Cocaine Sympathomimetics: Dopamine Dextroamphetamine Diethylpropion 2013 Omnipath, Inc. All rights reserved. 5

6 Dobutamine Terbutaline Pseudoephedrine Phenylpropanolmine Methylphenidate Isoproterenol Isoetharine Fenfluramine Phendimetrazine Etaraminol Metaproterenol Mazindol Methamphetamine Phentermine Phenylephrinephenmetrazine Albuterol Guanethidine Antihypertensive/ Cardiovascular Drugs: Bretylium Diltiazem Nifedipine Verapamil Reserpine 2013 Omnipath, Inc. All rights reserved. 6

7 DOSIMETRY 131 I has a longer physical half-life and higher gamma energy than 123 I. Additionally, 131 I emits a negatron and 123 I does not. 2 Refer to Table 4 for the radionuclidic properties of 131 I and 123 I. By comparing the radionuclidic properties of 131 I and 123 I, it is easy to see why the radiation dosimetry for 131 I-mIBG is greater than 123 I-mIBG on a per mci basis. Table 4: Properties of I-131 and I-123 2,7 I-131 I-123 Decay Mode Beta minus, gamma Electron capture, gamma Physical T 1/2 8.1 days 13.2 hr Photon Energy 364 kev 159 kev Photon Abundance 81% 83.4% β - Energy (Maximum) 606 kev Due to the high radiation dosimetry from 131 I-mIBG 7, the usual adult dosage was 0.5 mci with a maximum administered dosage being 1.0 mci. 8 The lower activity administered also provided poorer counting statistics as compared to 123 I-mIBG. Because of the favorable dosimetry from 123 I, 7 the recommended maximum administered activity for 123 I-mIBG for adults ( 16 years of age) is 10 mci. 9 Since 10 mci can be administered, the result is superior photon density of 123 I as compared to 131 I. 1 Refer to Tables 5 and 6 for radiation dosimetry for 131 I-mIBG and 123 I-mIBG. It is easy to understand why 131 I mibg, with its higher dosimetry along with the lower amount of radioactivity that can be administered, has gone by the wayside in favor of 123 I-mIBG Omnipath, Inc. All rights reserved. 7

8 Table 5: I-131 mibg Dosimetry 8 Organ rad/500 mci mgy/18.5 MBq Adrenal Medulla Heart Wall Liver Ovaries Spleen Thyroid (unblocked)* Testes Urinary Bladder Wall Total Body * By administered stable iodide as an adjunctive pharmaceutical, the radiation dosimetry to thyroid will be reduced to approximately 1% to 2% Omnipath, Inc. All rights reserved. 8

9 Table 6: I-123 mibg Dosimetry for Adults 9 Neuroendocrine Tumor Scintigraphy Organ rad/1 mci µgy/37 MBq rad/10 mci Adrenals Liver Ovaries Spleen Thyroid Testes Urinary Bladder Wall Effective Dose msv/mci 13.7 µsv/mbq 5.07 msv/10 mci 2013 Omnipath, Inc. All rights reserved. 9

10 IMAGING PROTOCOL RADIOPHARMACEUTICAL DOSAGE 123 I-mIBG is approved by the FDA for use as an adjunctive diagnostic drug in the localization of primary or metastatic pheochromocytoma and neuroblastoma. 10 According to the package insert, the 123 I-mIBG dosage for patients 16 years of age or less than 16 years of age but weigh 70 kg is 10 mci (370 MBq). For patients less than 16 years of age and weighing less than 70 kg, the dosage is scaled to adult reference dosage based on weight. 9 Gelfand reported that in his clinic, the pediatric dosage range of 123 I-mIBG is mci/kg to mci/kg. 11 The method of administration is by slow intravenous infusion over a time period of one to two minutes. To ensure complete delivery of the radiopharmaceutical, a subsequent injection of 0.9% sodium chloride may follow the 123 I-mIBG administration. 9 Before and intermittently for 30 minutes post administration of radioiodinated mibg, the patient s pulse and blood pressure should be carefully monitored because of the risk of hypertension due to possible increase in the release of norepinephrine from chromaffin granules. However, hypertension was not observed during the clinical study of 123 I-mIBG. 9 CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS 123 I-mIBG is contraindicated in patients having a known hypersensitivity to iobenguane or iobenguane sulfate. Following administration of 123 I-mIBG, hypersensitivity reactions have been reported. Prior to administration of the radiopharmaceutical, it should be determined if the patient is known or strongly suspected of having a hypersensitivity to iodine or iodine containing products. The decision to inject 123 I-mIBG is based upon an evaluation of the expected benefits versus the potential hypersensitivity risks. Hypersensitivity and anaphylactic treatment measures must be available prior to radiopharmaceutical administration. 9 In the 211 patients enrolled in GE Healthcare s clinical study of 123 I-mIBG, adverse reactions during the 24 hours post radiopharmaceutical administration were mild to moderate in severity and were principally isolated occurrences (< or = 2 patients). These reactions included dizziness, rash, pruritis, flushing, or injection site hemorrhage. During this time period there were no reports of serious adverse reactions. 10 The commercial preparation of 123 I-mIBG contains benzyl alcohol which has the potential to cause serious reactions in premature or low birth-weight infants. Following administration of the radiopharmaceutical, an infant should be observed for signs or symptoms of benzyl alcohol toxicity. The safety and efficacy of this product has not been established in pediatric patients below the age of one month Omnipath, Inc. All rights reserved. 10

11 ADJUNCTIVE PHARMACEUTICAL Free radioactive iodide may disassociate from the radioiodinated mibg, and this can concentrate in the thyroid gland. 6 In order to block the thyroid gland, patients are given potassium iodide (KI) at least one hour prior to administration of radioiodinated mibg. 9 To block the uptake of radioactive iodide by the patient s thyroid gland, Potassium Iodide Oral Solution or Lugol s Solution (equivalent to 100 mg for adults; for children, the dosage is adjusted based on body-weight) should be administered. An alternative thyroid blocking agent is potassium perchlorate in a dosage of 400 mg for adults (dosage for children adjusted according to body-weight). 9 Refer to Table 7 for a comparison of potassium iodide products. In order to lessen gastric irritation, potassium iodide should be given with milk, fruit juice, or a large volume of water. 12 Table 7: Comparison of Various Potassium Iodide (KI) Preparations 12 KI Preparations Quantity of KI Potassium iodide tablets 65 mg/tablet Potassium iodide tablets 130 mg/tablet Saturated solution of potassium iodide (SSKI) 1 gram/ml or 130mg/0.13 ml Lugol s solution 130 mg/0.8 ml 2013 Omnipath, Inc. All rights reserved. 11

12 MIBG IMAGING FOR NEUROENDOCRINE TUMORS TIME OF IMAGING AND VIEWS After injection of 123 I-mIBG, imaging can begin as early as 4 hours even though images acquired at 24 hours are of better-quality. 2 At 24 hours, whole-body image acquisition is utilized; however, SPECT is routinely added when enhanced image detail is necessary. 1 When a pheochromocytoma is suspected, posterior adrenal views are acquired at 24, 48, or 72 hours, if necessary. For the detection of adrenal medullary neuroblastoma and its metastatic lesions, whole-body imaging is obtained 24 and 48 hours post administration of 123 I-mIBG. Optimal visualization of skeletal and marrow metastatic lesions is usually at 48 hours. 4 POTENTIAL PROBLEMS There are numerous drugs that can decrease the sensitivity of a radioiodinated mibg study so it is critical that an adequate drug history be obtained. Refer to Tables 1, 2, and 3 for the recommended length of time these interfering drugs should be withheld. It has also been suggested that there are possibly some foods that could cause false-negative radioiodinated mibg studies. Those that have been suggested are vanillin containing foods and catecholamine-like compounds (chocolate and blue-veined cheeses). 6 Detection of neuroblastoma metastases may be hampered with aggressive chemotherapy. 4 Without administration of a thyroid-blocking agent, the radiation dose to the thyroid gland will be greater. 7 The possible adverse effects associated with the administration of potassium iodide are allergic reactions, minor rashes, and gastrointestinal disturbances. 12 Even though a thyroid-blocking agent can be administered to protect the thyroid gland from dissociated radioiodide, the radiolabeled mibg molecules appear to localize in the thyroid gland. 1 The patient in figure 1 was referred to nuclear medicine to evaluate for pheochromocytoma. The patient was intravenously administered 123 I-mIBG and imaged at 24 and 48 hours post injection. A mibg avid tissue was visualized in the region of the left adrenal gland; however, no other abnormal radiopharmaceutical uptake was noted Omnipath, Inc. All rights reserved. 12

13 Figure 1: 123I-mIBG avid tissue is demonstrated in the region of the left adrenal gland. CLINICAL APPLICATIONS NORMAL MIBG BIODISTRIBUTION It is normal for 123 I-mIBG to be taken up in the salivary glands and liver and to have faint radioactivity in the thyroid gland and heart. Renal and urinary bladder activity is apparent due to the drug undergoing renal excretion. In some patients activity is seen in the nasal area, neck muscle region, and bowel. Also, diffuse lung activity may also be visualized in some patients. Occasionally the normal adrenal medulla is demonstrated; however, it is best visualized in delayed images in approximately 30% to 40% of patients. The intensity of the normal adrenal medulla uptake is typically less than the liver; it must be differentiated from the greater abnormal uptake visualized in pheochromocytoma or neurobalstoma Omnipath, Inc. All rights reserved. 13

14 PHEOCHROMOCYTOMA These tumors are principally found in the adrenal medulla, and in the United States approximately 800 cases are diagnosed each year. 1 The usual positive scintigram demonstrates a unilateral focal uptake in the tumor; however, pheochromocytoma is bilateral in about 10% of the patients. With 10% to 20% of the patients, tumors are found outside of the adrenal glands, and these are known as paragangliomas. These extra-adrenal tumors may be detected from the urinary bladder to the base of the skull. Radioiodinated mibg scintigraphy is not a screening procedure, and it should be utilized only after the diagnosis has been suggested by biochemical tests. When the whole body needs to be surveyed for extra-adrenal tumors and metastatic disease, mibg imaging is very helpful. Imaging with radioiodinated mibg is distinctively useful in the detection of adrenal hyperplasia, and this nuclear medicine procedure has been employed to aid in determining timing of surgery. 2 For the detection of pheochromocytoma, radioiodinated mibg has a sensitivity of about 90%, and the sensitivity of 123 I-mIBG has been reported to slightly higher than with 131 I-mIBG. 6 NEUROBLASTOMA Neuroblastoma is one of the most frequent solid malignant tumors in children. 13 For the assessment of neuroblastoma, mibg scintigraphy is excellent since the sensitivity is approximately 90% 1 and specificity comes close to 100%. 1,13 Radioiodinated mibg is used to localize adrenal medullary neuroblastoma and its metastatic sites; and these lesions are demonstrated as foci of increased radioactivity. 4 It is routine to perform whole body imaging for patients with this disease. 2 Marrow and skeletal metastatic sites are typically visualized best 48 hours after 123 I-mIBG administration. 4 Since skeletal neuroblastoma metastatic lesions initially involve the bone marrow, radioiodinated mibg imaging has greater sensitivity for detection of these metastases than 99m Tc-diphosphonate bone scintigraphy. 2 Neither mibg imaging nor 99m Tc-medronate imaging alone identifies all lesions. In some patients mibg imaging is positive while the bone scintigraphy is negative, while in others the opposite is true. 13 However, when the findings of these two types of imaging procedures are combined, the highest sensitivity for detection of skeletal metastases is achieved. 2 Therefore, the initial evaluation should include both mibg imaging as well as diphosphonate bone imaging. It has been noted that mibg is useful in evaluating the treatment response of both primary and metastatic sites. Diphosphonate imaging is of limited value for follow-up because it is rare to find new sites of abnormal diphosphonate uptake without corresponding uptake of mibg. Also, such abnormalities on diphosphonate imaging are highly non-specific and may correlate to lesions not related to neuroblastoma Omnipath, Inc. All rights reserved. 14

15 Sharp et al conducted a study comparing the diagnostic utility of 123 I-mIBG and 18 F-FDG in 60 neuroblastoma patients (113 paired 123 I-mIBG and 18 F-FDG scans). They concluded that 18 F- FDG is superior in demonstrating stage 1 and 2 neuroblastoma; however, 123 I-mIBG may be necessary to rule out higher-stage disease. Also, they concluded that in patients whose tumors weakly accumulate 123 I-mIBG as well as in patients at major decision junctures during therapy ( i.e., before surgery or before stem cell transplantation), 18 F-FDG provides important information. They stated that while 18 F-FDG can better depict the extent of disease in the chest, abdomen, and pelvis; 123 I-mIBG is superior overall in the evaluation of stage 4 neuroblastoma, particularly during initial chemotherapy. This is principally due to the better detection of bone or marrow metastases with 123 I-mIBG. 14 OTHER TUMORS Carcinoid tumors and some medullary carcinomas of the thyroid also localize mibg, but the sensitivity for tumor detection is less than for pheochromocytoma or neuroblastoma. 2 With carcinoid tumors, radioiodinated mibg has good sensitivity (percentages in the 80s), but the sensitivity is only 30% to 55% for medullary thyroid cancer Omnipath, Inc. All rights reserved. 15

16 AUTHOR INFORMATION: Vivian S. Loveless, Pharm.D., BCNP, FAPha Associate Professor, Pharmaceutical Sciences College of Pharmacy The University of Tennessee Memphis, Tennessee REFERENCES 1. Alazraki NP, Shumate MJ, Kooby DA. Neuroendocrine cancers. In: A Clinician s Guide to Nuclear Oncology: Practical Molecular Imaging and Radionuclide Therapies. Reston, VA: The Society of Nuclear Medicine, Inc; 2007: Ziessman HA, O Malley JP, Thrall JH. Endocrine system. In: Thrall JH, ed. Nuclear Medicine: The Requisites in Radiology. 3 rd ed. Philadelphia, PA: Elsevier Mosby; 2006: Kowalsky RJ, Falen SW.Total-body and miscellaneous procedures. In: Kowalsky RJ, ed. Radiopharmaceuticals in Nuclear Pharmacy and Nuclear Medicine. 2 nd ed. Washington, D.C.: American Pharmacists Association; 2004: Mettler FA, Jr, Guiberteau MJ. Genitourinary system and adrenal glands. In: Essentials of Nuclear Medicine Imaging. 5 th ed. Philadelphia, PA: Saunders Elsevier; 2006: Omnipath, Inc. All rights reserved. 16

17 5. Shapiro B. Clinical atlas: I-131 MIBG (iobenguane sulfate I-131 injection) scintigraphy for localization of pheochromocytoma. In: Shapiro B and Hoefnagel CA, eds. Clinical Use of I-131 MIBG Scintigraphy (Iobenguane Sulfate I-131 Injection) in Localization of Pheochromocytoma and Neuroblastoma. Bedford, MA: CIS-US Inc; pp Taylor A, Schuster DM, Alazraki N. Neuroendocrine tumors. In: A Clinician s Guide to Nuclear Medicine. 2 nd ed. Reston, VA: The Society of Nuclear Medicine, Inc; 2006: Shulkin BL, Shapiro B. Current concepts on the diagnostic use of MIBG in children. J Nucl Med 1998; 39: Iobenguane Sulfate I 131 Injection Diagnostic For Intravenous Use [package insert]. Bedford, MA: CIS-US Inc, March AdreView TM Iobenguane I 123 injection [package insert]. Arlington Heights, IL: GE Healthcare, September Iobenguane I (accessed on 08/05/09). 11. Gelfand MJ. Meta-iodobenzylguanidine in children. Semin Nucl Med 1993; 23: Kowalsky RJ, Falen SW.Thyroid. In: Kowalsky RJ, ed. Radiopharmaceuticals in Nuclear Pharmacy and Nuclear Medicine. 2 nd ed. Washington, D.C.: American Pharmacists Association; 2004: Omnipath, Inc. All rights reserved. 17

18 13. Olivier P, Colarinha P, Fettich J, et al. Guidelines for radioiodinated MIBG scintigraphy in children. Eur J Nucl Med Mol Imaging 2003; 30:BP45-BP Sharp SE, Shulkin BL, Gelfand MJ, et al. 123 I-MIBG scintigraphy and 18 F-FDG PET in neuroblastoma. J Nucl Med 2009; 50: Omnipath, Inc. All rights reserved. 18

19 TEST QUESTIONS QUESTION #1 Which of the following characterizes the decay of I-123? Electron capture Emission of a 364 x-ray Emission of a negatron Physical T ½ of 8.1 hours QUESTION #2 What is the package insert s recommended dosage of 123 I-mIBG for a 17 y/o weighing 160 pounds? 0.5 mci 1.0 mci 10 mci 22.4 mci QUESTION #3 What is the recommended length of time that labetalol should be withheld prior to the administration of radioiodinated mibg? 1 week 2 weeks 3 weeks 6 weeks 2013 Omnipath, Inc. All rights reserved. 19

20 QUESTION #4 According to the package insert for iobenguane I 123, what is the recommended dosage of potassium iodide necessary to block the adult thyroid from uptake of iodine I23? 16 mg 65 mg 100 mg 400 mg QUESTION #5 In order to protect the thyroid gland, potassium iodide should be given the administration of radioiodinated mibg? 1 hour before 2 hours after 1 day before At the time of imaging QUESTION #6 The majority of pheochromocytomas are found in the: Adrenal medulla Liver Spleen Thyroid gland 2013 Omnipath, Inc. All rights reserved. 20

21 QUESTION #7 Which organ receives the greatest radiation dose after administration of 123 I- mibg to a normal subject? Adrenal medulla Blocked thyroid Liver Spleen QUESTION #8 After the administration of 123 I-mIBG, there is a possibility of an increase in release of norepinephrine from chromaffin granules which could result in a transient increase in blood pressure. Thus, the patient s pulse and blood pressure should be monitored: Before and intermittently for 30 minutes post administration Immediately after injection and at the time of imaging Prior to and 5 minutes after radiopharmaceutical administration One hour before and one after administration QUESTION #9 The FDA approved iobenguane I 123 as adjunct diagnostic test in the detection of: Adrenal cortex tumor Carcinoid tumor Medullary carcinoma Neuroblastoma 2013 Omnipath, Inc. All rights reserved. 21

22 QUESTION #10 mibg scintigraphy for neuroblastoma has a specificity approaching: 55% 80% 90% 100% 2013 Omnipath, Inc. All rights reserved. 22