(68)Ga-DOTATATE PET/CT imaging of indeterminate pulmonary nodules and lung cancer

PURPOSE: (18)F-FDG PET/CT is widely used to evaluate indeterminate pulmonary nodules (IPNs). False positive results occur, especially from active granulomatous nodules. A PET-based imaging agent with superior specificity to (18)F-FDG for IPNs, is badly needed, especially in areas of endemic granulomatous nodules. Somatostatin receptors (SSTR) are expressed in many malignant cells including small cell and non-small cell lung cancers (NSCLCs). (68)Ga-DOTATATE, a positron emitter labeled somatostatin analog, combined with PET/CT imaging, may improve the diagnosis of IPNs over (18)F-FDG by reducing false positives. Our study purpose was to test this hypothesis in our region with high endemic granulomatous IPNs. METHODS: We prospectively performed (68)Ga-DOTATATE PET/CT and (18)F-FDG PET/CT scans in the same 30 patients with newly diagnosed, treatment-naïve lung cancer (N = 14) or IPNs (N = 15) and one metastatic nodule. (68)Ga-DOTATATE SUVmax levels at or above 1.5 were considered likely malignant. We analyzed the scan results, correlating with ultimate diagnosis via biopsy or 2-year chest CT follow-up. We also correlated (68)Ga-DOTATATE uptake with immunohistochemical (IHC) staining for SSTR subtype 2A (SSTR2A) in pathological specimens. RESULTS: We analyzed 31 lesions in 30 individuals, with 14 (45%) being non-neuroendocrine lung cancers and 1 (3%) being metastatic disease. McNemar’s result comparing the two radiopharmaceuticals (p = 0.65) indicates that their accuracy of diagnosis in this indication are equivalent. (68)Ga-DOTATATE was more specific (94% compared to 81%) and less sensitive 73% compared to 93%) than (18)F-FDG. (68)Ga-DOTATATE uptake correlated with SSTR2A expression in tumor stroma determined by immunohistochemical (IHC) staining in 5 of 9 (55%) NSCLCs. CONCLUSION: (68)Ga-DOTATATE and (18)F-FDG PET/CT had equivalent accuracy in the diagnosis of non-neuroendocrine lung cancer and (68)Ga-DOTATATE was more specific than (18)F-FDG for the diagnosis of IPNs. IHC staining for SSTR2A receptor expression correlated with tumor stroma but not tumor cells.