Can Hybrid SPECT-CT Overcome the Limitations Associated With Poor Imaging Properties of 131 I-MIBG? Comparison With Planar Scintigraphy and SPECT in Pheochromocytoma Punit Sharma, MD, Varun Singh Dhull, MD, Sunil Jeph, MD, Rama Mohan Reddy, MD, Harmandeep Singh, MD, Niraj Naswa, MD, Chandrasekhar Bal, MD, and Rakesh Kumar, MD, PhD Objective: This study aimed to evaluate the incremental value of 131 I-MIBG hybrid SPECT-CT over planar scintigraphy (PS) and SPECT alone in patients with clinical or biochemical suspicion of pheochromocytoma. Methods: A total of 126 adrenals of 63 patients (mean [SD] age, 28.6 [15.7] years; male patients, n = 34; female patients, n = 29) with clinical or biochemical suspicion of pheochromocytoma were retrospectively evaluated. All patients had undergone 131 I-MIBG SPECT-CT of adrenal region. The PS, SPECT, and SPECT-CT images were independently evaluated by 2 nuclear medicine physi- cians with 6 years (R1) and 2 years (R2) experience and in separate sessions 1 week apart. A scoring scale of 1 to 5 was used, in which 1 is definitely abnormal, 2 is probably abnormal, 3 is indeterminate, 4 is probably normal, and 5 is defi- nitely normal. Sensitivity, specificity, predictive values were calculated taking a score 2 or less as abnormal. With receiver operating characteristic (ROC) curve analysis, areas under the curve (AUC) were calculated for each modality and compared. Histopathology and/or clinical/imaging follow-up were taken as ref- erence standard. Results: Of the 126 adrenals evaluated, 29 were indeterminate on PS for R1 and 48 for R2, 39 were indeterminate on SPECT for both, and on SPECT-CT, 1 was indeterminate for R1 and 2 for R2. SPECT-CT correctly characterized 28 of 29 indeterminate adrenals on PS and 37 of 39 indeterminate adrenals on SPECT for R1. Similarly, for R2, SPECT-CT correctly characterized 45 of 48 indeter- minate adrenals on PS and 33 of 39 indeterminate adrenals on SPECT. On ROC comparison, PS was inferior to SPECT (P = 0.040 for R1; P G 0.001 for R2) and SPECT-CT (P = 0.001 for R1; P G 0.001 for R2) for both the observers. Moreover, SPECT was inferior to SPECT-CT for both the observers (P = 0.017 for R1 and P = 0.001 for R2). Accuracy of SPECT-CT (R1, 97.6%; R2, 97.6%) was higher than PS (R1, 91.2%; R2, 84.1%) and SPECT (R1, 94.4%; R2, 86.5%). Interobserver agreement was highest for SPECT-CT (J = 0.966) as compared with PS (J = 0.815) and SPECT (J = 0.826). Conclusions: 131 I-MIBG hybrid SPECT-CT shows high sensitivity and speci- ficity for characterizing adrenal lesions in patients with clinical or biochemical suspicion of pheochromocytoma and is superior to PS and SPECT alone. It will be especially useful in countries where 123 I-MIBG is not available. Key Words: 131 I-MIBG, planar scintigraphy, SPECT, SPECT-CT, pheochromocytoma (Clin Nucl Med 2013;00: 00Y00) P heochromocytomas are catecholamine-producing neuroendocrine tumors arising from chromaffin cells of the adrenal medulla or extraadrenal paraganglia. Nearly 80% to 85% of pheochromocytomas arise from the adrenal medulla, whereas approximately 15% to 20% are from extraadrenal chromaffin tissue. 1 The prevalence of pheo- chromocytoma in patients with hypertension is 0I1% to 0I6%. 2 Al- though these tumors are frequently searched for, they are rarely found. The diagnosis is usually based on combination of clinical symptoms and biochemical results. Traditional biochemical tests include mea- surements of urinary and plasma catecholamines, urinary metanephrines (normetanephrine and metanephrine), and urinary vanillylmandelic acid. Measurements of plasma-free metanephrines (normetanephrine and metanephrine) represent a more recently available test. 3 Because surgery is the treatment of choice for pheochromocy- toma, accurate preoperative localization is vital. Tumor localization should ideally only be initiated once there is unequivocal biochem- ical evidence for pheochromocytoma. CT or MRI is most often used for initial localization of pheochromocytoma. Because of comparable sensitivities of CT and MRI (90%Y100%) and risks associated with contrast injections and radiation exposure associated with CT, MRI should be preferred. 4 The specificity of CT and MRI is limited; there- fore, adrenal masses demonstrated on these techniques are usually evaluated with MIBG scintigraphy, which is considered the criterion standard. 5 MIBG is a structural and functional analog of norepineph- rine and guanethidine that selectively accumulates in the noradrenergic neurosecretory granules of chromaffin tissue. Uptake is proportional to granule density. 6 MIBG can be labeled with either 131 I or 123 I. For imaging, 123 I-MIBG is preferred over 131 I-MIBG because of better imaging characteristics and favorable dosimetry of 123 I-MIBG. 7,8 Be- cause of its poor resolution, 131 I-MIBG scintigraphy is often false neg- ative for small and necrotic lesions. Unfortunately, 123 I-MIBG is costly, is not available in many countries including India, and cannot be imported because of short half life of 123 I(T 1/2 = 13 hours). SPECT-CT has been shown to be very useful for characterizing indeterminate planar scintigraphy findings for bone, hepatobiliary sys- tem, and parathyroids, with high accuracy. 9Y11 Addition of SPECT-CT has also been shown to improve the accuracy of 123 I-MIBG scintigra- phy for diagnosis of pheochromocytoma. 12,13 However, no such study is available for 131 I-MIBG. Hence, we designed this study to investigate whether hybrid SPECT-CT can overcome the limitations associated with poor imaging properties of 131 I MIBG and thus can be used as an alternative to 123 I-MIBG in patients with suspicion of pheochromocy- toma. We also assessed the incremental value of 131 I MIBG SPECT-CT over planar scintigraphy and SPECT alone. PATIENTS AND METHODS Patients This was a retrospective analysis and was approved by the institutional review board. Between May 2010 and December 2011, a total of 72 patients with clinically and/or biochemically suspected pheo- chromocytoma underwent 131 I-MIBG scintigraphy with SPECT-CT of upper abdomen. Data of these 72 patients were evaluated. We excluded ORIGINAL ARTICLE Clinical Nuclear Medicine & Volume 00, Number 00, Month 2013 www.nuclearmed.com 1 Received for publication July 1, 2012; revision accepted September 10, 2012. From the Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India. Conflicts of interest and sources of funding: none declared. Reprints: Rakesh Kumar, MD, PhD, Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India, E-81, Ansari Nagar (East), AIIMS Campus, New Delhi-110029, India. E-mail: rkphulia@yahoo.com. Copyright * 2013 by Lippincott Williams & Wilkins ISSN: 0363-9762/13/0000Y0000 Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.