Comparison of 99m Tc-HYNIC-TOC and HYNIC-TATE Octreotide Scintigraphy With FDG PET and 99m Tc-MIBI in Local Recurrent or Distant Metastatic Thyroid Cancers Sait Sager, MD,* Levent Kabasakal, MD,* Metin Halac, MD,* Helmut Maecke, PhD,Þ Lebriz Uslu, MD,* C ¸etin O ¨ nsel, MD,* and Bedii Kanmaz, MD * Aim: There have been various studies for early diagnosis of local recurrent or distant metastatic thyroid cancers. The aim of this study is to evaluate the clinical utility of 99m Tc-HYNIC-TOC and 99m Tc-HYNIC-TATE, octreotide de- rivatives, to detect recurrences or distant metastases in 131 I-negative thyroglob- ulin positive thyroid cancer patients and to compare the lesions with FDG PET and 99m Tc-MIBI studies in the same patient group. Patients and Methods: Twenty differentiated thyroid cancer patients, 7 male and 13 female, mean age 54.6 T 15.3 (range 13Y78 years), were included in this study. Eighteen patients had papillary thyroid cancer and 2 had follicu- lar thyroid cancer. Fifteen patients received HYNIC-TOC and 5 patients received HYNIC-TATE as a radiopharmaceutical. All patients underwent whole-body scan 1 and 4 hours after injection of octreotide derivatives and SPECT imagings were performed from the suspicious sites. The lesions that were seen in 99m Tc-HYNIC-TOC and 99m Tc-HYNIC-TATE studies were compared with 99m Tc-MIBI and FDG-PET studies. Results: Among 99m Tc-HYNIC-TOC and 99m Tc-HYNIC-TATE scintigra- phies, 15 patient studies were evaluated as true positive (75%) and 5 were false negative (25%). The total number of lesions in octreotide scintigra- phy was 48 in 20 patients. Of 20 patients, 19 had FDG-PET study, 15 of them were evaluated as true positive (78.9%), and 4 them were evaluated as false negative (21.1%). Total number of lesions in FDG PET was 74. 99m Tc-MIBI study was positive in 11 patients (55%) and negative in 9 patients (45%). Total number of lesions in 99m Tc-MIBI was 25. Conclusion: Technetium-labeled somatostatin receptor scintigraphy analogues HYNIC-TOC and HYNIC-TATE are useful imaging alternatives in somato- statin receptor expressing thyroid cancer patients. Radiolabeling is easy and they are readily available for routine use. Key Words: Octreotide scintigraphy, HYNIC-TOC, HYNIC-TATE, FDG PET, 99m Tc-MIBI (Clin Nucl Med 2013;38: 321Y325) T hyroid cancer is the most common malignancy of the endocrine system, and the incidence of thyroid carcinoma in the United States has been increasing since 1980. Based on rates from 2007 to 2009, 1.03% of men and women born today will be diagnosed with cancer of the thyroid at some time during their lifetime. 1 The inci- dence of thyroid cancer in young adults is also rising. Differentiated thyroid carcinoma (DTC) (papillary, follicular) and medullary thy- roid carcinoma (MTC) represent the 2 most common subtypes, with differing etiologies, prognoses, and management strategies. 2 Despite the increase in its incidence, there is a decrease in thyroid cancerY related mortality. Its increased incidence is related to improved di- agnostic methods, whereas decreased mortality is a result of early diagnosis, new therapy methods, and decreased incidence of ana- plastic subtype of thyroid carcinoma. 3 In patients with differentiated thyroid cancer, who had undergone total thyroidectomy and radioiodine (RAI) ablation therapy, if whole-body scintigraphy with radioiodine ( 131 I-WBS) is negative despite elevated thyroglobulin (Tg) levels, the site of recurrence or distant metastases might be difficult for de- tection. To detect the site of recurrence in these group of patients, conventional diagnostic tools, namely ultrasonography (USG), CT, and MRI, as well as 99m Tc-MDP bone scan, 201 Tl scan, 99m Tc-labeled isonitrile compounds, such as sestamibi and tetrafosmin, octreotide scintigraphy, PET, and PET/CT can be used. 4Y6 The aim of this study was to compare 99m Tc-octreotide scin- tigraphy with 99m Tc-MIBI WBS and FDG PET/CT to detect the sen- sitivity and specificity of 99m Tc-octreotide derivatives in patients with differentiated thyroid carcinoma, whose 131 I-WBS were negative de- spite elevated thyroglobulin levels. FDG PET 18 F-FDG PET/CT plays a crucial role in the detection of re- sidual tumor mass in patients with differentiated thyroid carcinoma, especially in iodine-negative, Tg-positive patients. It has an impor- tant role in patients with Tg level higher than 10 ng/mL and negative 131 I-WBS after total thyroidectomy and RAI ablation. 7 Diagnostic ability of FDG PET is improved in patients with elevated TSH levels in comparison to patients with suppressed TSH levels. 8 Thyroid can- cer related mortality increases in patients with metastases detected with FDG PET, high SUV max values, and increased volume of lesions. 9 MIBI If 131 I-WBS is negative in differentiated thyroid carcinoma patients with elevated Tg levels, 99m Tc-methoxy isobutyl isonitrile ( 99m Tc-MIBI) WBS can be used. Its uptake is directly proportional to blood flow and mitochondria concentration. It can also be performed in patients with suppressed TSH levels, which is the major advan- tage of MIBI imaging. 10 Octreotide Scintigraphy Somatostatin scintigraphy is most commonly used in evalua- tion of somatostatin receptorYpositive tumors. 11 There are 5 different subtypes of somatostatin receptors, and natural somatostatin can bind to all of them. Synthetic somatostatin analogue octreotide can bind to somatostatin receptor subtype 2 strongly and to subtype 5 weakly. 12 111 In-labeled octreotide scintigraphy [(In-111-diethylenediaminopen- toacetic acid-D-Phe 1 -octreotide) (Octreoscan; Mallinckrodt Medical, Petten, the Netherlands)] is the most common somatostatin analogue. 111 In-octreotide scintigraphy is a widely used method to reveal neu- roendocrine tumors and other somatostatin receptorYpositive tu- mors. However, there are some disadvantages related to 111 In, such as limited access, high cost, suboptimal image resolution due to medium energy, and high radiation burden to the patient. Therefore, ORIGINAL ARTICLE Clinical Nuclear Medicine & Volume 38, Number 5, May 2013 www.nuclearmed.com 321 Received for publication May 8, 2012; and revision accepted December 29, 2012. From the *Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey; and †Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany. Conflicts of interest and sources of funding: none declared. Reprints: Sait Sager, MD, Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul University, Cerrahpasa, Fatih, Istanbul, Turkey. E-mail: saitsager@yahoo.com. Copyright * 2013 by Lippincott Williams & Wilkins ISSN: 0363-9762/13/3805Y0321 Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.