Superiority of [68Ga]-DOTATATE PET/CT to Other Functional Imaging Modalities in the Localization of SDHB-Associated Metastatic Pheochromocytoma and Paraganglioma

Abstract

Purpose Patients with succinate dehydrogenase subunit B (SDHB) mutation-related pheochromocytoma/paraganglioma (PHEO/PGL) are at a higher risk for metastatic disease than other hereditary PHEOs/PGLs. Current therapeutic approaches are limited but the best outcomes are based on the early and proper detection of as many lesions as possible. Because PHEOs/PGLs overexpress somatostatin receptor 2 (SSTR2), the goal of our study was to assess the clinical utility of [68Ga]-DOTA(0)-Tyr(3)-octreotate ([68Ga]-DOTATATE) positron emission tomography/computed tomography (PET/CT) and to evaluate its diagnostic utility in comparison to the currently recommended functional imaging modalities [18F]-fluorodopamine ([18F]-FDA), [18F]-fluorodihydroxyphenylalanine ([18F]-FDOPA), [18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG) PET/CT as well as CT/magnetic resonance imaging (MRI). Experimental Design [68Ga]-DOTATATE PET/CT was prospectively performed in 17 patients with SDHB-related metastatic PHEOs/PGLs. All patients also underwent [18F]-FDG PET/CT and CT/MRI with 16 of the 17 patients also receiving [18F]-FDOPA and [18F]-FDA PET/CT scans. Detection rates of metastatic lesions were compared between all these functional imaging studies. A composite synthesis of all used functional and anatomical imaging studies served as the imaging comparator. Results [68Ga]-DOTATATE PET/CT demonstrated a lesion-based detection rate of 98.6% (95% confidence interval (CI) 96.5% to 99.5%), [18F]-FDG, [18F]-FDOPA, [18F]-FDA PET/CT, and CT/MRI showed detection rates of 85.8% (CI 81.3% to 89.4%) (p<0.01), 61.4% (CI 55.6% to 66.9%) (p<0.01), 51.9% (CI 46.1% to 57.7%) (p<0.01), and 84.8% (CI 80.0% to 88.5%) (p<0.01), respectively. Conclusions [68Ga]-DOTATATE PET/CT showed a significantly superior detection rate compared to all other functional and anatomical imaging modalities and may represent the preferred future imaging modality in the evaluation of SDHB-related metastatic PHEO/PGL.

Functional Imaging Signature of Patients Presenting with Polycythemia/Paraganglioma Syndromes

“…All CT and MRI scans of the neck, chest, abdomen, and pelvis were obtained as follows and previously described (13). CT scans of the neck, chest, abdomen, and pelvis were obtained using the following devices: Somatom Definition AS and Somatom Definition Flash (Siemens Medical Solutions) and Aquilion ONE (Toshiba Medical Systems).…”

“…As previously described and supported (13,14), a positive result on at least 2 different functional imaging modalities, or at least 1 functional imaging study and confirmation on CT/MRI, was counted as true disease. Furthermore, histologic proof was available for 18 lesions.…”

“…When histologic proof was neither feasible nor ethical for lesion detection, the composite of both anatomic and all functional imaging tests was considered the imaging comparator, as previously described and supported (13,14).…”

Genotype–phenotype Correlation in Children with Pheochromocytoma and Paraganglioma

“…17 A recent study has also demonstrated the superiority of 68 Ga-DOTATATE PET/CT in SDHBrelated metastasis over the previously mentioned functional imaging methods. 18 The 18 F-FDG PET/CT can differentiate SDHx-related HNPGL from sporadic ones with 80% accuracy. 19 However, no such data are available in children.…”

“…In adults, it has been shown that 18 F-fluro-deoxy-glucose (FDG) positron emission tomography/computerized tomography (PET/CT) and 18 F-fluro-dopamine PET are more sensitive in detecting metastasis in SDHB mutation carriers, whereas 18 F-fluro-dihydroxyphenylalanine PET/CT is more useful to detect non SDHB metastasis. 17 A recent study has also demonstrated the superiority of 68 Ga-DOTATATE PET/CT in SDHBrelated metastasis over the previously mentioned functional imaging methods.…”