Original Benign Pathologies and Variants with 68ga-Dotatate Uptake in PET/CT Studies L. Servente, C. Bianco, V. Gigiret and O. Alonso Centro Uruguayo de Imagenología Molecular, CUDIM, Montevideo, Uruguay Abstract Purpose: To evaluate the physiological, anatomical variants and benign lesions in positron emission computed tomog- raphy (PET/CT) studies with 68Ga-DOTATATE. Materials and methods: We retrospectively reviewed reports of 68Ga-DOTATATE PET/CT scans and selected those that contained words in the report related to anatomical, physiological variants and benign tumors. The degree of 68Ga-DOTATATE uptake was qualitatively and quantitatively evaluated by measuring the standardized uptake max value (SUVmax value). The anatomical location, SUVmax value and morphological computed tomography (CT) image findings were recorded. All cases had a clinical and imaging follow-up. Results: From a total of 772 PET/CT reports, we obtained 28 patients with 33 benign variants or tumors, 14 females and 14 males with a median age of 63 years. Uptake patterns were classified into four groups: anatomic and physi- ological variants (n = 15), dependent on osteoblastic activity (n=4), dependent on inflammatory activity (n=10) and non-neuroendocrine benign tumors (n=4). Discussion: Somatostatin receptors are overexpressed not only in the neuroendocrine system but also in other tissues. Physiological, anatomical variants and benign tumors expressing these receptors may be misleading. Conclusion: Physiological variants and benign lesions (tumor and inflammatory lesions) can accumulate 68Ga-DOT- ATATE since their tissues can express somatostatin receptors. The semiological analysis of the tomographic component of this hybrid imaging method enhances the diagnostic efficacy, optimizing PET/CT study performance. © 2017 Sociedad Argentina de Radiología. Published by Elsevier Spain, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Keywords: 68-Gallium DOTATATE; Positron emission tomography/computed tomography; Somatostatin receptors; Hy- brid imaging Introduction The biodistribution of this tracer shows the highest uptake in the spleen, followed by adrenal glands, the pituitary gland Positron emission tomography combined with computer to- and the kidney. In decreasing order of uptake intensity, these mography (PET/CT) using 68 Gallium (68Ga)-DOTATATE, a are followed by the liver, salivary glands and the thyroid6,7. radioactively labeled somatostatin (SST) analog, is a first-line The uptake in the stomach, small and large bowel is variable hybrid imaging method for the evaluation of patients with because of neuroendocrine cell hyperplasia. In the pancreas, well-differentiated neuroendocrine tumors (NET) for local- the presence of a larger number of cells expressing soma- izing the primary tumor, staging-restaging tumors and se- tostatin receptors has been reported, mainly in the pancreatic lecting patients for radionuclide therapy1-4. This method has head and in the uncinate process6,8,9. also been used in the imaging of granulomatous and auto- As there is an overlap in uptake intensity between benign and immune conditions as well as of other non-neuroendocrine malignant lesions, it is essential to know the anatomic, physi- tumors, although in these cases it cannot be considered as ologic variants and benign entities that most frequently occur the first-choice functional imaging modality3,5. as findings unrelated to the underlying tumor. Somatostatin receptors are distributed in the whole body. The aim of this study is to consider the physiologic, anatomic Normal tissues and benign diseases (benign tumors or in- variants and benign lesions in PET/CT scans with 68Ga-DOT- flammatory conditions) can also express these receptors and ATATE that may constitute potential sources of diagnostic error. therefore can also show increased uptake of this tracer. 184 Rev. Argent. Radiol. 2017;81(3): 184-191 L. Servente et al. Materials and methods droma, inflammatory, uncinate, accessory spleen, splenosis, prostatitis, fracture, accessory, reactive, dysplasia, fibrous. Patients gave their written informed consent authorizing the use of their scans and clinical data for scientific purposes; Image acquisition data were anonymized. Because of its retrospective design, 68Ga-DOTATATE was injected at a dose of 2.5 MBq/kg of the study was not submitted to the Ethics Committee. weight. At 30 minutes post-injection, 3D images were ac- quired by PET/CT with and without tomography attenuation Selection of scans correction on 16- and 64-slice General Electric (GE) hybrid We retrospectively reviewed a total of 772 reports of 68Ga- scanners (Discovery STE and 690 Discovery, respectively). DOTATATE PET/TC scans performed to 639 patients between Images were recorded from the skull to the middle third of June 2011 and June 2016. A search was performed in the site the femoral shaft for 120 seconds/bed for the STE Discovery database for the following keywords mentioned in reports: scanner and for 90 seconds/bed for the 690 Discovery scan- hemangioma, angioma, schwannoma, meningioma, enchon- ner. Computed tomography (CT) was performed with 80-180 Table 1: Description of indication, gender, age, SUVmax and findings. Patient # FINDING SUV 1 SUV 2,3 AGE GENDER INDICATION 1 Paget 6.4 79 M Prostate cancer 2 Fracture 6.7 34 M Oncogenic osteomalacia 3 Echondroma 3.8 53 F NETUP 4 Accessory spleen 18.8 65 F Gastrointestinal NET 5 Accessory spleen 14 60 M NETUP 6 Accessory spleen 17.4 13 M Gastrointestinal NET 7 Splenosis 21 70 F Pancreatic NET 8 Splenosis 10 56 F Pancreatic NET 9 Duodenum variant 10 44 M Adrenal carcinoma 10 Pancreas variant 12.5 21 M Multicenter ganglioneuroma, MEN syndrome 11 Pancreas variant 9.6 70 F Gastrointestinal NET 12 Pancreas variant/accessory spleen 8.3 13.1 56 F Insulinoma 13 Uterine uptake 4.4 63 F Gastrointestinal NET 14 Uterine uptake 5.7 44 F NETUP 15 Uterine uptake 4.6 76 F Pancreatic NET 16 Uterine uptake/ degenerative disc disease 9.1 6.7 54 F NETUP 17 Bone hemangioma 7.9 51 M Gastrointestinal NET 18 Bone hemangioma 6.6 57 M Prostate cancer 19 Hemangioma/fracture/inflammatory 3.9 4.3/4.1 74 F Medullary thyroid carcinoma 20 Lymph node chronic inflammation 5.5 41 M Mediastinal adenopathies 21 Lymph node chronic inflammation 3.7 24 M Mediastinal adenopathies 22 Postoperative chronic inflammation 7.1 66 M Gastrointestinal NET 23 Degenerative disc disease/accessory spleen 6.1 22 65 F Invasive thymoma / insulinoma 24 Prostatitis 5.9 63 M Gastrointestinal NET 25 Cerebral falx meningioma 5.1 69 F Breast cancer, dural lesion 26 CPA meningioma 3.1 64 M NETUP 27 Cerebral falx meningioma 5.2 72 M Pulmonary NET 28 Left C4 schwannoma 8.8 69 F Gastrointestinal NET Patient # 1 to 3: findings dependent on osteoblastic activity. Patients # 4 to 16: anatomic and physiological variants. Patients # 17 to 24: chronic inflammation. Patients # 25 to 28: non-neuroendocrine tumors. Ca: cancer; MEN 1: multiple endocrine neoplasia syndrome 1, NETUP: neuroendocrine tumor of unknown primary, NET: neuroendocrine tumor. Rev. Argent. Radiol. 2017;81(3): 184-191 185 Benign Pathologies and Variants with 68ga-Dotatate Uptake in PET/CT Studies mA, 120 kV (noise index, 20) and 3.75-mm slice thickness, experience in hybrid imaging. pitch 1,375 and table movement 27.5 mm per rotation for Data were recorded on uptake location, SUVmax value, the STE Discovery scanner and 17.5 mm per rotation for the oth- CT morphological image, age, gender, the reason for per- er scanner. Emission data were processed by iterative recon- forming the PET scan, the use of radiological contrast and struction (OSEM). All patients received an oral contrast agent follow-up. An electronic datasheet was prepared. and the intravenous (IV) contrast only when indicated by the Histological confirmatory tests were performed in two pa- imaging specialist. No late phase imaging was performed. tients: CT-guided aspiration in one patient and laparotomy in the other. In all other patients benign findings were con- Evaluation of images firmed by their clinical course and an imaging follow-up (CT, Axial, coronal and sagittal images as well as maximum-in- MRI or PET/CT) between 6 months and 6 years, with an aver- tensity projection (MIP) images were evaluated. The degree age follow-up of 1 year. of 68Ga-DOTATATE uptake was evaluated by a qualitative and quantitative visual analysis, with the latter being done by maximum standardized uptake value (SUVmax) measure- Results ment. Images were analyzed on GE Advantage workstations, versions 4.5 and 4.6. The scans were reviewed jointly by two Out of 772 reports performed during a 5-year period (corre- physicians: a nuclear medicine specialist and a radiology spe- sponding to 639 patients), 101 contained the keywords listed cialist, both certified and with 5 years’ experience in conven- above. Reports in which the keyword was unrelated to the tional nuclear medicine and radiology and at least 2 years’ aim of our study were excluded. Figure 1 Patient # 10. Male, 21 years old. Left adrenal multicentric ganglioneuroma resection. Multiple endocrine neoplasia syndrome. Physiological variant of the uncinate process. (a) MIP PET image shows abdominal focal uptake (arrow), (b) Axial PET image and (c) fused PET/CT image with IV contrast: focal uptake in uncinate process (arrow) SUVmax 12.5. 186 Rev. Argent. Radiol. 2017;81(3): 184-191 L. Servente et al. Figure 2 Patient # 8. Female, 56 years old, caudal pancreatectomy and splenectomy for NET of the pancreatic tail. PET/CT scan for restaging. Splenosis. (a) Axial fused PET/CT image shows focal uptake in splenosis (arrow). SUVmax 10, (B) MIP PET image shows focal uptake (arrow). Figure 3 Patient # 3. Female, 53 years old. Carotid adenopathy resection. Pathology examination reported neuroendocrine metastasis. PET/CT for localization of the primary tumor. Finding: enchondroma. (a) Coronal CT: left femoral intertrochanteric lesion.